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Introduction: Female hormones and obesity have an impact on women with asthma. We aimed to describe how these components affect asthma inflammatory processes., Methods: Sex hormones [FSH, LH, estradiol (E2), estrone (E1), testosterone and Δ4 androstenedione (A4)] and serum IL1β, IL13, IL17a, IL-5, IL6, TNF-a were measured from 11 to18 pre- and postmenopausal women with asthma., Results: Premenopausal normal weight women revealed higher levels of IL5 and IL17a than obese women on both days of the menstrual cycle (IL5: D1: 6.4 vs 1.4 pg/ml, p  = .036 and D14: 3 vs 1.4 pg/ml, p  = .045 and IL17a: D1: 13.7 pg/ml vs 10.6 pg/ml and D14: 12.4 pg/ml vs 10.6 pg/ml, p  = .009, respectively). In premenopausal women on D1, Δ4 Androstenedione was positively correlated with IL1β ( p  = .016, r  = 0.733), whereas on D14, Estradiol with IL1β ( p  = .009, r = -.768) and TNF-a with Testosterone ( p  = .004, r = -0.816), and Δ4 Androstenedione ( p  = .002, r = -0.841) negatively. In postmenopausal women, TNF-a was negatively associated with FSH ( p  = .004, r = -0.638), but positively with Testosterone ( p  = .025, r  = 0.526) and IL10 also positively with Estradiol ( p  = .007, r  = 0.610)., Conclusion: Obesity shows a protective role in asthma through the suppression of IL5 and IL17. Estrogens seem to inhibit Th1 and Th2 inflammation, while androgens have a dual role with negative and positive correlations with neutrophilic biomarkers.

In studies investigating the etiology and pathophysiology of autism spectrum disorder (ASD), immune dysregulation is commonly observed, with elevated levels of inflammatory cytokines frequently found in gestational tissues. However, studies investigating the relationship between early immune dysregulation within the umbilical cord blood (CB) compartment and neurodevelopmental outcomes remains limited. In this exploratory study, we utilized data from the prospective Markers for Autism Risk in Babies - Learning Early Signs (MARBLES) study to examine cytokine levels in the plasma fraction of CB in infants later diagnosed with ASD (n = 38) compared to infants typically developing (TD) at age 3 years (n = 103), using multiplex cytokine assays. Our findings reveal altered levels of several inflammatory cytokines in children later diagnosed with ASD, including increased granulocyte colony-stimulating factor (G-CSF) and decreased interleukin-1α (IL-1α), IL-1β, and IL-4 in CB. Furthermore, we identified several associations between behaviors and levels of cytokines, chemokines and growth factors. IL-1α, IL-17A, interferon γ-induced protein 10 (IP-10), and epidermal growth factor (EGF) were associated with worse scores on Autism Diagnostic Observation Schedule (ADOS) and the Mullen Scales of Early Learning (MSEL) assessments. In summary, our study demonstrates dysregulated levels of inflammatory cytokine mediators in the CB of children later diagnosed with ASD and that inflammatory mediators were associated with ASD severity, comorbid behaviors, and neurodevelopmental measures. These findings have important implications for the possible predictive value of early cytokine measures in neurodevelopmental outcomes and subsequent behavioral manifestations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Genetic factors, including the Hedgehog Interacting Protein (HHIP) gene, play a crucial role in Chronic Obstructive Pulmonary Disease (COPD) susceptibility. This study examines the association between HHIP gene polymorphisms and COPD susceptibility, phenotypes, and serum IL-17 and IL-18 levels in a Han Chinese population., Methods: A case-control study was conducted with 300 COPD patients and 300 healthy controls in Chinese Han population. Participants underwent genotyping for HHIP gene polymorphisms, pulmonary function tests, and quantitative CT scans. DNA samples were sequenced using a custom chip targeting the HHIP gene. Serum IL-17 and IL-18 levels were measured by enzyme-linked immunosorbent assay. Associations between SNPs, COPD susceptibility, and phenotypes were analyzed using logistic and multiple linear regression models, adjusting for confounders., Results: Our study identified the rs11100865 polymorphism in the HHIP gene as significantly associated with COPD susceptibility (OR 2.479, 95% CI 1.527-4.024, P = 2.39E-04) after screening 114 SNPs through rigorous quality control. Stratified analyses further indicated this association was particularly in individuals aged 60 or older. Serum levels of IL-17 and IL-18 were significantly elevated in COPD patients compared to controls, with rs11100865 showing a notable association with IL-18 levels (B = 49.654, SE = 19.627, P = 0.012). However, no significant associations were observed between rs11100865 and serum IL-17 levels, COPD-related imaging parameters, or clinical phenotypes., Conclusion: This study identified a significant association between HHIP gene polymorphisms and COPD susceptibility in a Han Chinese population, with connections to inflammation, but found no significant associations between this SNP and COPD-related imaging or clinical phenotypes., Trial Registration: www.chictr.org.cn ID: ChiCTR2300071579 2023-05-18., (© 2024. The Author(s).)

Amidst the existing literature on the effect of isotretinoin on serum interleukin-17 levels in acne patients, the effects of oral antibiotics azithromycin and doxycycline on serum interleukin-17 is scarce. We conducted an investigator blinded randomized interventional study to compare the effect of doxycycline, azithromycin and isotretinoin on inflammatory markers and Interleukin-17A (IL-17A) levels in acne. Patients were randomized and received the treatment according to treatment arm till 12 weeks. At baseline and 12 weeks/treatment completion, clinical improvement and Red-cell-distribution width (RDW),Neutrophil-lymphocyte ratio(NLR),Platelet-lymphocyte ratio(PLR), Mean-Platelet volume(MPV), Platelet-distribution width(PDW) and Interleukin-17A levels were analysed. P-value < 0.05 was considered statistically significant. Out of 120 patients, 110 patients completed the study. Baseline Global acne grading scale (GAGS) in doxycycline, azithromycin or isotretinoin group was 24.32  ± 3.119, 24.12 ± 2.804 and 25.10 ± 3.985 respectively and post-treatment was 5.216  ± 1.88, 7.265 ± 2.17 and 2.769 ± 1.08. All the drugs caused a statistically significant decrease in RDW and IL-17 A levels. Baseline levels of IL-17 A were significantly higher in patients with higher GAGS and post-acne scarring. One of the limitations of our study was that we excluded severe nodulocystic acne patients thereby these results have to be carefully extrapolated., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Neutrophil extracellular traps (NETs) are produced by polymorphonuclear neutrophils (PMNs) stimulated by interleukin-17 (IL-17) and tumor necrosis factor α (TNF-α). However, the level and role of NETs in oral lichen planus (OLP) remain poorly understood., Objective: This study aimed to investigate the expression of NETs in OLP and explore the correlation between NETs and the levels of IL-17 and TNF-α., Methods: The expression and distribution of NET-related proteins in tissue samples from each group were assessed using hematoxylin-eosin (HE) staining and immunofluorescence (IF). Additionally, the expression of NET-related proteins in peripheral blood samples from each group was evaluated using cell IF technique and fluorescence spectrophotometry. The relative formation level of NETs in each group was determined by fluorescence spectrophotometry via plasma co-culture. Furthermore, the levels of inflammatory cytokines IL-17 and TNF-α in plasma and culture supernatant were measured using enzyme-linked immunosorbent assay (ELISA)., Results: NET-related proteins were located in the subepithelial and lamina propria layers of OLP lesions. OLP had significantly higher expression of NET-related proteins in lesion tissues and peripheral blood compared to the healthy control (HC) group ( p < 0.05). The rate of NETs formation in the erosive-stage OLP (EOLP) group was significantly higher than that in the HC group ( p < 0.05), in contrast, no significant increase was observed in the non-erosive OLP (NEOLP) group ( p > 0.05). Furthermore, the levels of IL-17 and TNF-α in the EOLP group were significantly elevated compared to those in the NEOLP group and HC group ( p < 0.05), while the levels in the NEOLP group did not significantly differ from those in the HC group ( p > 0.05). The rate of NETs formation showed a positive correlation with the levels of IL-17 and TNF-α in plasma., Conclusion: The expression of NET-related proteins was upregulated in OLP lesion tissues and peripheral blood. Elevated levels of IL-17 and TNF-α in peripheral blood plasma positively correlated with the rate of NETs formation, suggesting that IL-17 and TNF-α mediate the formation of NETs in OLP patients, and may thereby contribute to the development of OLP., Competing Interests: The authors declare that they have no competing interests., (© 2024 Cheng et al.)

The overexpression of interleukin-17A (IL-17A) is closely associated with the pathogenesis of autoimmune diseases and cancer, rendering precise identification of IL-17A level critical for disease diagnosis and prognosis monitoring. In this study, CsPbBr 3 nanoclusters (NCs) were embedded in C 16 H 14 Br 2 O 6 Pb 2 organometallic compound (Pb-MA MOC) via a hot injection approach. Through this way, the issue of CsPbBr 3 NCs susceptible to decomposition in water was solved, and the photocurrent intensity that is generated by CsPbBr 3 was significantly enhanced. A highly sensitive photoelectrochemical (PEC) sensor for detecting IL-17A in human serum was developed using CsPbBr 3 /Pb-MA as the photoactive material. The electrode was initially modified with CsPbBr 3 /Pb-MA. Then, antibody-modified Fe 3 O 4 magnetic nanoparticles (MNs) with target analyte IL-17A captured, and IL-17A antibody-modified Au@CuNi diatomic catalyst (DAC) formed sandwich immune complex structure on the electrode. The existence of CuNi DAC led to a substantial reduction in photoelectric signal intensity due to oxidation of ascorbic acid in the supporting electrolyte. The photocurrent intensity exhibited linear correlation with IL-17A concentration within the range 15-750 pg/mL, and achieving an impressive detection limit of 1 pg/mL. Moreover, the sensor was successfully applied to the determination of IL-17A in human serum, suggesting its potential clinical applications., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Respiratory tract infections are a common health problem. Cytokines/chemokines play a critical role in the regulation of the immune system. Their defective production may predispose to recurrent respiratory tract infections (RRIs), and an excessive immune response may lead to chronic inflammation and cause damage to the respiratory tract. Another biomarker of respiratory infections may be immunoglobulin-IgG4. Its meaning has still been little explored. We wanted to assess the suitability of the levels of biomarkers tested: interleukin (IL)-17A, IL-18, IL-23, normal T cells expressed and secreted (RANTES), and induced protein (IP)-10, as well as immunoglobilun G4 (IgG4) to predict recurrent infections. Methods: The study group (SG) included a total of 130 children (68 girls, 62 boys) between 3 and 17 years of age with RRI. The control group (CG) included 86 healthy children with no symptoms of inflammatory or allergic diseases (44 girls and 42 boys) of the same age. Blood samples were collected in fasting state and then serum samples were frozen and stored until biomarker assay. Results: Serum RANTES, IL-18, IL-23, and IgG4 concentration were higher in all children with recurrent infections vs. those in the CG ( p   < 0001). Serum levels of IL-17A and IP-10 were also significantly higher in the SG than in the CG, but only in the youngest children. Among the six serum markers, RANTES demonstrated the highest area under the receiver operating characteristic curve (area under curve) value (0.998, 95% confidence interval [CI]: 0.98-1.0, p < 0.001) for the diagnosis of RRIs, followed by IL-23 (0.99, 95% CI 0.966-0,999, p < 0.001) and IL-18 (0.957, 95% CI 0.921-0.980, p < 0.001). Conclusions: RANTES, IL-23, and IL-18 could be strong predictors of respiratory infections recurrence in children., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Edyta Machura et al.)

Background: Major psychotic disorders (MPD), including schizophrenia (SCZ) and schizoaffective disorder (SAD), are severe neuropsychiatric conditions with unclear causes. Understanding their pathophysiology is essential for better diagnosis, treatment, and prognosis. Recent research highlights the role of inflammation and the immune system, particularly the Interleukin 17 (IL-17) family, in these disorders. Elevated IL-17 levels have been found in MPD, and human IL-17 A antibodies are available. Changes in chemokine levels, such as CCL20, are also noted in SCZ. This study investigates the relationship between serum levels of IL-17 A and CCL20 in MPD patients and their clinical characteristics., Method: We conducted a case-control study at the Ibn Sina Psychiatric Hospital (Mashhad, Iran) in 2023. The study involved 101 participants, of which 71 were MPD patients and 30 were healthy controls (HC). The Positive and Negative Symptom Scale (PANSS) was utilized to assess the symptoms of MPD patients. Serum levels of CCL20 and IL-17 A were measured using Enzyme-Linked Immunosorbent Assay (ELISA) kits. We also gathered data on lipid profiles and Fasting Blood Glucose (FBS)., Results: The mean age of patients was 41.04 ± 9.93 years. The median serum levels of CCL20 and IL-17 A were significantly elevated in MPD patients compared to HC (5.8 (4.1-15.3) pg/mL and 4.2 (3-5) pg/mL, respectively; p < 0.001). Furthermore, CCL20 and IL-17 A levels showed a positive correlation with the severity of MPD. MPD patients also had significantly higher FBS, cholesterol, and Low-Density Lipoprotein (LDL) levels, and lower High-Density Lipoprotein (HDL) levels compared to HC. No significant relationship was found between PANSS components and blood levels of IL17 and CCL20., Conclusion: The current study revealed that the serum levels of IL-17 A and CCL20 in schizophrenia patients are higher than those in the control group. Metabolic factors such as FBS, cholesterol, HDL, and LDL also showed significant differences between MPD and HC. In conclusion, the findings suggest that these two inflammatory factors could serve as potential therapeutic targets and prognostic biomarkers for schizophrenia., (© 2024. The Author(s).)

Aim: An excessively activated or dysregulated complement system has been proven to be a vital contributor to the pathogenesis of periodontitis. It has been previously hypothesized that inhibiting the activity of complement component C5 by targeting the C5a receptor is a powerful candidate for treating periodontitis. Here, we apply the drug target instrumental variable (IV) approach to investigate the therapeutic effect of genetically proxied inhibition of C5 on periodontitis., Method: In our primary analysis, we used 26 independent 'cis' single nucleotide polymorphisms as IVs from the vicinity of the encoding locus of C5 that are associated with plasma C5 levels. In a secondary analysis, we assess the validity of our primary findings, exploring the involvement of alternative downstream biomarkers, interleukin 17 (IL-17), interleukin 1β (IL-1β), and tumor necrosis factor (TNF). Summary statistics of plasma levels (C5, IL-17, IL-1β, and TNF) were obtained from a genome-wide association study (GWAS) of 35,559 European descent individuals. We extracted association statistics from a GWAS of 17,353 clinical periodontitis cases and 28,210 European controls. Wald ratios were combined using inverse-variance weighted meta-analysis., Results: In our primary approach, inhibiting C5 reduced the risk of periodontitis (Odds ratio 0.89 per 1 standard deviation reduction in C5; 95% confidence Interval 0.80-0.98, p value=0.022). Our secondary analysis suggests an involvement of IL-17 within the potential causal pathway, but was inconclusive for other biomarkers., Conclusions: The findings from our study suggest that C5 inhibition may reduce the risk of periodontitis, prioritizing C5 inhibitors as a potential adjunctive therapeutic intervention in this disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Alayash, Baumeister, Holtfreter, Kocher, Baurecht, Ehmke, Reckelkamm and Nolde.)

Background: Mucosal-associated invariant T (MAIT) cells play key roles in many inflammatory diseases. However, their effects on the long-term course of oral lichen planus (OLP) and recent-onset OLP remain unclear. In this study, we aimed to investigate the function of MAIT cells in the different processes of OLP and to explore the immunological background of this disease., Methods: The frequency, phenotype, cytokine secretion, and clinical relevance of MAIT cells were investigated. MAIT cells were collected from the peripheral blood of 14 adults with recent-onset OLP (7-120 days after disease onset) and 16 adults with long-term course OLP (>2 years after diagnosis) using flow cytometry and compared with 15 healthy blood donors. Statistical analyses were performed using the GraphPad Prism software., Results: MAIT cells from adults with recent-onset OLP exhibited an activated phenotype, as indicated by an increased frequency of CD69 + (p < 0.05) and CD38 + MAIT cells (p < 0.01) and elevated production of the proinflammatory cytokine IL-17 A (p < 0.01), compared with healthy adult donors. In adults with long-term OLP, MAIT cells exhibited an activated and exhausted phenotype, characterized by high expression of CD69 (p < 0.01) and PD-1 (p < 0.001) and increased production of granzyme B released (p < 0.01). Compared with recent-onset OLP patients, long-term OLP patients showed a decreased production of CD8 + , and CD4 - CD8 - cells, but an increase in PD-1 + production (p < 0.05)., Conclusions: Circulating MAIT cells exhibited activation in OLP patients across varying disease durations. Given that PD-1 expression is elevated in adults with long-term OLP, it is reasonable to infer that circulating MAIT cells in long-term OLP may exhibit a more exhausted state than those in recent-onset OLP., (© 2024. The Author(s).)

Primary knee osteoarthritis (KOA) is a persistent condition marked by the gradual deterioration of the joint and cartilage loss on its surfaces. Recently, platelet-rich plasma (PRP) was considered a biological intervention that alleviates symptoms and restricts the advancement of primary KOA in patients. This study aimed to evaluate the effect of intra-articular PRP injections on synovial repair through cytokine assays in 20 patients with primary KOA. Patients received two intra-articular PRP injections, spaced one month apart. The role of PRP was assessed by measuring Transforming growth factor beta (TGF-β) and interleukin-17 (IL-17) levels in synovial fluid before and after the injections. Both visual analogue scale and Western Ontario and McMaster Universities Osteoarthritis index were assessed before and after intervention. IL-17 and TGF-β levels were measured in the synovial fluid using sandwich ELISA technique before the first PRP intra-articular injection and one month after the second injection to assess the synovial repair after PRP injection. Our results showed that the synovial IL-17 levels significantly decreased by 75.21% (p < 0.0001) after intra-articular knee injection, dropping from a range of 102.3-293 (median 173.5: 139.7- 224.5) to 17.86-106 (median 36.38: 23.57- 50.32). In contrast, synovial TGF-β levels significantly increased by 80.3% (p < 0.0001) after intra-articular knee injection, rising from 124-545.5 (mean ± SD: 256.22 ± 123.56) to 693.3-3226 (mean ± SD: 1521.6 ± 765.46). In conclusion, intra-articular PRP administration in primary KOA patients is associated with increased levels of TGF-β and decreased levels of IL-17 in the synovial fluid of the joint. These changes in cytokine levels suggest that PRP treatment effectively reduces inflammation and may contribute to pain relief in primary KOA., (Copyright© by the Egyptian Association of Immunologists.)

Background: Endothelial dysfunction is an integral pathophysiologic mechanism in sickle cell disease (SCD), and can lead to many complications. Sleep-disordered breathing (SDB) is a SCD complication with diverse incidence and pathophysiology. This study aimed to determine the prevalence of SDB in children with SCD and to assess its relation to endothelial dysfunction., Methods: Sixty children with SCD and 60 healthy controls were enrolled. The levels of TNF-α, IL-6, and IL-17A were evaluated in the entire cohort using enzyme-linked immunosorbent assay (ELISA) kits. Polysomnography (PSG) was performed for all SCD patients after completion of the Pediatric Sleep Questionnaire (PSQ)., Results: TNF-α, IL-6, and IL-17A levels were significantly greater in children with SCD than in controls (p-values < 0.001, < 0.001, and 0.006, respectively). The PSQ revealed symptoms suggestive of SDB in 50 children with SCD (83.3%), and PSG revealed obstructive sleep apnea (OSA) in 44 children with SCD (73.3%); 22 patients had mild OSA, and 22 had moderate-to-severe OSA according to the apnea-hypopnea index (AHI). TNF-α was significantly greater in SCD children who reported heavy or loud breathing, trouble breathing or struggle to breathe, and difficulty waking up in the morning (p-values = 0.002, 0.002, and 0.031, respectively). The IL-6 levels were significantly greater in SCD children who stopped growing normally (p-value = 0.002). The levels of IL-6 and IL-17A were significantly greater in SCD children with morning headaches (p-values = 0.007 and 0.004, respectively)., Conclusion: Children with SCD showed a high prevalence of SDB with significantly elevated levels of markers of endothelial function, highlighting the interplay of SDB and endothelial dysfunction in SCD., (© 2024. The Author(s).)

Thyroid eye disease (TED) is expressed as orbital inflammation, and serum levels of several proinflammatory cytokines have been studied among patients with Graves' disease (GD) with and without TED; however, a more sensitive and specific marker for the different phases of GD and TED is still lacking. Seventeen active TED, 16 inactive TED, 16 GD without TED, and 16 healthy controls were recruited. Serum IL-17A, MMP-2, MMP-3, and MMP-9 were measured by multiplex bead assay. TED hormone and eye parameters were evaluated, and their relationship with cytokine levels was analyzed. Serum MMP-9 was higher in active TED than healthy controls, whereas IL-17A was lower among these patients than in GD without TED and healthy controls. No differences were found in MMP-3 and MMP-2 concentrations. MMP-9 levels were lower in patients with inactive TED who underwent radioactive iodine (RAI) therapy and those on levothyroxine replacement. MMP-9 levels were elevated in patients on methimazole. A negative correlation was found between age at assessment and time of follow-up with MMP-9 levels in inactive TED. Free T3 and ophthalmometry values were positively correlated with MMP-9 in the GD without TED and inactive TED groups, respectively. In conclusion, serum MMP-9 was increased in patients with active TED and was related to the RAI treatment, longer follow-up time, and higher ophthalmometry in patients with inactive TED, as well as thyroid function in GD without TED. MMP-9 may be involved in both the active phase of TED and the active phase of inflammation related to GD. NEW & NOTEWORTHY Our study addresses clinical aspects of specific ophthalmological examination and serum cytokine concentrations of patients with Graves' disease (GD) with and without ophthalmopathy. Our findings suggest that MMP-9 may be involved in the active phase of ophthalmopathy and in the active phase of GD. The central question is whether MMP-9 is a potential target for future treatments.

Objective: Inflammation plays an important role in epilepsy. There is evidence for the relationship between proinflammatory cytokines and epilepsy. We aimed to detect the serum levels of multiple cytokines in epilepsy patients, looking for biological indicators, and providing a theoretical basis for the clinical diagnosis, treatment, and prognosis of epilepsy., Materials and Methods: In this study, 30 patients with drug-resistant epilepsy (DRE), 30 patients with well-controlled epilepsy (WCE), and 29 healthy controls (HC) were enrolled. Multi-proinflammatory cytokines were measured by LUMINX multi-factor detection., Results: The levels of IL-1β, IL-7, IL-12, and IL-17 were significantly elevated, and the levels of CX3CL1 and ITAC were significantly decreased in epilepsy patients compared with healthy controls. Furthermore, the level of IL-17 was significantly higher in the DRE group compared to WCE. We also found the ratio of IL-7/CX3CL discriminates accurately between patients and controls, with a ROC Area Under the Curve (AUC) of 0.963 (P<0.001). The levels of IL-1β, IL-7, IL-12, and IL-17 in the DRE group were positively correlated with the National Hospital Seizure Severity Scale (NHS3) scores (IL-1β, P = 0.029; IL-12, P = 0.039; IL-17, P = 0.004). IL-17 was positively correlated with seizure frequency (P = 0.050), while ITAC was negatively correlated with seizure frequency (P = 0.012) and Sudden Unexpected Death in Epilepsy-3 (SUDEP-3) scores (P = 0.023)., Conclusions: IL-1β, IL-12, and IL-17 may be used to predict seizure severity and the IL-7/CX3CL1 ratio may be a candidate biomarker for predicting epileptic seizures. While CX3CL1 and ITAC play anti-epileptic effects, ITAC may be used to assess the risk of SUDEP., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Inflammatory bowel disease (IBD) is characterized by recurrent inflammation of the gastrointestinal tract and has been linked to an imbalance in gut bacteria. Synbiotics, which combine probiotics and prebiotics, are emerging as potential IBD treatments., Aim: To examine the effects of four synbiotic formulations on intestinal inflammation and peripheral biomarkers in a rodent IBD model of both sexes., Methods: Colitis was induced in male and female C57BL/6 mice using 1% dextran sulfate sodium (DSS). Concurrently, a non-exposed control group was maintained. Starting on day 4 post-induction, DSS-exposed mice received one of four synbiotic preparations (Synbio1-4 composed of lactic acid bacteria, Bifidobacterium and dietary fibres), an anti-inflammatory drug used to treat IBD (mesalazine), or placebo (water) until day 14. Clinical symptoms and body weight were monitored daily. Blood samples (taken on days -3, 4, and 14, relative to DSS introduction), were used to analyze plasma biomarkers. At the end of the study, intestinal tissues underwent histological and morphological evaluation., Results: Compared to placebo, the Synbio1-, 2- and 3-treated groups had improved clinical scores by day 14. Synbio1 was the only preparation that led to clinical improvements to scores comparable to those of controls. The Synbio1-and 3-treated groups also demonstrated histological improvements in the colon. Plasma biomarker analyses revealed significant Synbio1-induced changes in plasma IL17A, VEGFD, and TNFRSF11B levels that correlated with improved clinical or histological scores. Sex-stratified analyses revealed that most therapeutic-like effects were more pronounced in females., Conclusion: Our findings underscore the potential therapeutic benefits of specific synbiotics for IBD management. However, further research is needed to validate these outcomes in human subjects., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Bronchial asthma (BA) is increasing among Egyptian children. It is affected by multiple factors including genetic ones. In the current study, we assessed the relationship between interleukin-17 ( IL-17 ) genotypes and the occurrence of BA among Egyptian children. This case-control study included 100 participants. Group I (the control group) comprised 50 healthy subjects. Group II (the asthmatic group) comprised 50 subjects diagnosed with atopic asthma according to the Global Initiative for Asthma. Measurement of serum Ig E and eosinophilic count was performed. Detection of single nucleotide polymorphism rs2275913 of IL-17 gene by restriction fragment length polymorphism-polymerase chain reaction was conducted. GA and AA genotypes were more frequent in the asthmatic group compared to the control group ( P = 0.03 and 0.01, respectively). Subjects carrying GA and AA genotypes were more susceptible to have asthma [odds ratio (OR) = 2.21, 95% confidence interval (CI) = 1.14-9.94, P = 0.03; OR = 7.78, 95% CI = 1.59-38.3, P = 0.01, respectively]. The A allele was higher in the asthmatic group (33%) compared to the control group (10%). A allele carriers were more susceptible to have asthma (OR = 4.43, 95% CI = 2.04-9.82 and P < 0.001). Immunoglobulin E (IgE) levels and eosinophil percentages were higher among the carriers of GA and AA genotypes when compared with the GG genotype. All pulmonary function tests were significantly lower among carriers of AA genotype compared with GG genotype. An A allele carrier, AA genotype, increased IgE level, and eosinophil level were significant predictors for occurrence of asthma ( P = 0.01, 0.02, 0.004, and 0.01). In conclusion, AA genotype carriers and A allele carriers of the IL-17 gene are more likely to have asthma compared with controls.

Ulcerative colitis (UC) is characterized by chronic inflammation of the large intestine with involvement of Th17 cells and interleukin (IL)-17A. The role of IL17A and IL17A receptor (IL17RA) variants in pathophysiology of UC still remains inconclusive. The aim was to evaluate the association between IL17A and IL17RA variants with susceptibility, IL-17A plasma levels, and endoscopic activity in UC. The study included 104 patients with UC and 213 controls. Patients were divided according to endoscopic activity (remission/mild and moderate/severe). The IL17A rs3819024 A>G and rs3819025 G>A, and IL17RA rs2241043 C>T, rs2241049 A>G, and rs6518661 G>A variants were genotyped using real time polymerase chain reaction. IL-17A plasma levels were determined using immunofluorimetric assay. Neither IL17A nor IL17RA variants were associated with UC susceptibility. The IL17A rs3819024 AG genotype was associated to high levels of IL-17 only in patients. Patients with the G allele of IL17RA rs2241049 showed 2.944 more chance of developing moderate/severe disease. The haplotype analysis showed that IL17RA rs2241049 and rs6518661 was not associated with UC susceptibility and haplotypes constituted with G allele of these variants were not associated with disease severity (p = 0.09). In conclusion, the IL17A rs3819024 AG genotype was associated with elevated IL-17A plasma levels in patients with UC but not in controls and the IL17RA rs2241049 AG+GG genotypes were associated to severity of UC. These results suggest a possible hidden interaction between the IL17A rs3819024 variant and other genetic, environmental, and epigenetic factors in the IL-17A expression that is present only in patients with UC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: To investigate the levels of 12 kinds of cytokines in seminal plasma and their correlations with routine semen parameters., Methods: The remaining seminal plasma samples of 134 patients undergoing routine semen examination were collected for detecting cytokines. The parameters for sperm concentration, percentage of progressively motile sperm (PR), and motility were analyzed by a computer-assisted sperm analysis (CASA) system. According to the results of sperm concentration, PR and motility, 134 patients were divided into the normal routine semen parameters group, oligoasthenospermia group and azoospermia group. The levels of 12 kinds of cytokines in seminal plasma, including interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17, interferin (IFN)-α, IFN-γ, and tumor necrosis factor (TNF)-α, were detected by flow cytometry. Two seminal plasma samples were detected for 10 times, respectively, to calculate the coefficients of variation (CV) of each cytokine. The linear range of each cytokine was measured using the standard, and the correlation coefficient (r) was calculated., Results: The r 2 of 12 kinds of cytokines detected by flow cytometry were all greater than 0.99. The reproducibility of 2 seminal plasma samples showed that the CVs of all cytokines were lower than 15 % except for TNF-α in sample 1 (15.15 %). Seminal plasma IL-6 levels were negatively correlated with semen volume (P < 0.01). Seminal plasma IL-5 levels were positively correlated with sperm concentration (P < 0.01). Seminal plasma IL-8 levels were negatively correlated with sperm motility (P < 0.01). Seminal plasma IL-8, IL-17 and IL-12P70 levels were negatively correlated with sperm PR (P < 0.05). In addition to the significant negative correlation between IL-5 and IL-17 (P < 0.05), there was a significant positive correlation between the majority of other cytokines. The levels of seminal plasma IL-17 and IL-12P70 in the oligoasthenospermia group and IL-1β and IL-12P70 in the azoospermia group were significantly higher than those in the normal routine semen parameters group (P ≤ 0.05), while the levels of IL-10 in the azoospermia group were significantly lower than that in the normal routine semen parameters group (P < 0.05)., Conclusion: There are certain correlations between seminal plasma cytokines and routine semen parameters and strong correlations between different seminal plasma cytokines, suggesting that the imbalance between seminal plasma cytokines may affect sperm quality. However, it still needs to be further confirmed by large samples and multi-center clinical studies and related basic researches., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Xia Zhao reports administrative support and article publishing charges were provided by Special Fund Project for Health Science and Technology Development of Nanjing Health Construction Commission. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Atopic dermatitis (AD) is the most prevalent chronic inflammatory skin disease in childhood. Interleukin 17 (IL17) is one of the pro-inflammatory cytokines that has an important role in the pathogenesis of many skin diseases including AD. Ischemia modified albumin (IMA) is an indicator of oxidative stress, inflammation and ischemia. The aim of the study was to assess the IL-17 and IMA serum levels in the children patients with AD in comparison to a control group. Additionally, the study seeks to examine the correlation between these biomarkers and their association with disease severity, disease stages, and other clinical characteristics., Methods: The case-control study enrolled two groups: (patient group: 50 children with AD) and (control group: 50 healthy age and sex-matched children). Full history was taken from all cases along with full dermatologic examination. The assessment of AD severity was conducted by using Eczema Area and Severity Index (EASI). Evaluation of IL-17 and IMA was performed by using ELISA technique., Results: There was a statistically significant elevation in the mean levels of IL-17 and IMA in patients with AD compared to the control group. A strong positive correlation was observed between IL-17 and IMA levels. Additionally, both IL-17 and IMA levels exhibited a statistically significant negative correlation with the duration of the disease and the age of the patients., Conclusion: The elevated serum levels of IL17 and IMA and their positive correlation confirm that AD is a systemic inflammatory disease influenced and associated with increased oxidative stress., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The aim of this study is to evaluate the role of serum level of Interleukin 6(IL-6) and Interleukin 17 (IL-17) in liver transplantation outcome for living recipients, Analyze the relation between the gene polymorphism and the occurrence of rejection after liver transplantation and Study the relation between the gene polymorphism and the occurrence of different infectious complications. The study was conducted in March 2023 and included 60 healthy volunteers from the National Liver Institute (NLI) blood bank at Menoufia University and 120 live donation liver recipient patients at NLI. During one month of liver transplantation, the cytokine levels (IL-17, IL-6 proteins, IL-6 G-174C, and IL-17 A rs2275913 gene polymorphism) and CD4 levels for 60 patients of 120 live donation liver recipient patients whom early reject transplanted tissue and the same parameters were measured after 6 months follow up for non-reject group. The main finding of this study was that the post-transplant rejection group and the post-transplant non-rejection and control groups differed significantly in the genotype frequency (CC, CG, and GG) or alleles of IL-6 G-174C (p = 0.011). On the other hand IL-17A rs2275913 gene polymorphism and its alleles (p = 0.71) showed no statistically significant difference. We also observed that serum IL-17 levels, with 100% specificity and 100% sensitivity threshold, will be more sensitive and specific than serum IL-6 and CD4 count in differentiating post-transplant rejection from non-rejection patients. The results showed that there was no significant relationship between the genotypes and serum levels of interleukins and the type and degree of rejection. Proinflammatory cytokines might be useful indicators for distinguishing and early identifying unfavorable outcomes after transplantation, allowing for prompt and effective treatment intervention. To evaluate these findings, prospective clinical trials are required., (© 2024. The Author(s).)

Objectives: To analyze the clinical significance of Toll-Like Receptor 7/Interleukin-23/Interleukin-17 (TLR7/IL-23/IL-17) signaling pathway in patients with Acute Respiratory Distress Syndrome (ARDS)., Method: The clinical data of 85 patients with ARDS were retrospectively analyzed and set as the ARDS group, and the clinical data of 85 healthy participants during the same period were set as the healthy control group. Univariate and multivariate logistic regression were used to analyze risk the factors affecting the prognosis of ARDS patients., Results: TheTLR7 mRNA expression and IL-23 and IL-17 levels in peripheral blood mononuclear cells were higher in the ARDS group than in the control group (p < 0.05). TLR7 mRNA expression, IL-23, IL-17, Surfactant Protein-D (SP-D), and Clara Cell protein-16 (CC-16) levels were the highest in the severe group, followed by the moderate group, and the lowest in the mild group, while Oxygenation Index (OI) was the lowest in the severe group, followed by the moderate group, and the highest in the mild group (p < 0.05). Multivariate logistic regression analysis found that the disease grade (severe), TLR7 mRNA expression, IL-23 level, and IL-17 level were the risk factors affecting the 28-d survival status of ARDS patients (OR > 1, p < 0.05)., Conclusions: In ARDS patients, the TLR7/IL-23/IL-17 signaling pathway is activated. The expression of this pathway is closely related to the severity of the disease and the levels of lung injury markers, and it is a risk factor that may have a direct impact on the prognosis of ARDS patients., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Psoriasis is a chronic inflammatory skin condition associated with systemic inflammation and a higher risk of cardiovascular comorbidities. This study retrospectively evaluates coagulation parameters in psoriasis vulgaris patients treated with IL-17 inhibitors (secukinumab, ixekizumab) and IL-23 inhibitors (risankizumab, guselkumab), compared to those untreated systemically. The study reviewed records from 177 patients treated between January 2019 and March 2023. Patients were grouped into control (n = 77), secukinumab (n = 36), ixekizumab (n = 19), guselkumab (n = 24), and risankizumab (n = 21). Coagulation parameters, including PT, aPTT, PLT, MPV, INR, fibrinogen, D-dimer, and B12 levels, were analyzed. The primary endpoint was the comparison of coagulation parameters between groups. Significant differences were found in PT, with secukinumab-treated patients showing a significantly shorter PT compared to controls (p = 0.002). No significant differences were observed in other coagulation parameters across the groups. The study highlights a potential effect of secukinumab on coagulation pathways, possibly related to IL-17's role in inflammation and endothelial function. Despite current literature suggest a risk of cerebrovascular events with risankizumab, this study did not show any significant changes in coagulation parameters with risankizumab, indicating no hypercoagulability risk associated with this IL-23 inhibitor. Our findings suggest IL-17 and IL-23 inhibitors are generally safe concerning coagulation parameters, but regular monitoring may be warranted for patients on secukinumab due to its effect on PT. Further long-term studies are needed to fully understand the cardiovascular risks associated with these therapies., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The mechanisms underlying subclinical hypothyroidism (SCH) remain unclear, making timely and accurate differentiation between hypothyroidism and SCH, as well as severity assessment, challenging. This study aimed to investigate the role of NFE2 like bZIP transcription factor 2 (Nrf2), gp 91phox , and interleukin-17 (IL-17) in the pathogenesis of SCH. In this prospective comparative study, 105 SCH patients, 105 hypothyroidism patients, and 105 healthy individuals were enrolled from January 2022 to August 2023. SCH patients were categorized into mild-moderate and severe groups based on thyroid-stimulating hormone (TSH) levels. Levels of TSH, free T4 (FT4), free T3 (FT3), thyroglobulin antibodies (TG-Ab), thyroid peroxidase antibodies (TPO-Ab), cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-ch), and low-density lipoprotein-cholesterol (LDL-ch) were measured. Nrf2, IL-1β, IL-6, IL-17, and gp 91phox levels were tested using ELISA. Nrf2, IL-17 and gp91 phox were significantly higher in SCH and hypothyroidism patients compared to the healthy controls, with hypothyroidism patients showing the highest levels. Nrf2 levels were negatively correlated with TSH, TG-Ab and IL-17, but not gp91 phox . Nrf2, IL-17 and gp91 phox could be used for diagnosis of SCH and severe SCH. Only TG-Ab, IL-17 and gp91 phox were independent risk factors for severe SCH. This study demonstrates a negative correlation between serum Nrf2 levels and SCH severity. TG-Ab, IL-17, and gp 91phox are independent risk factors, and their associations with SCH pathology suggest their potential roles in the disease mechanism. These findings provide insights into SCH pathogenesis and highlight the need for further research to elucidate their diagnostic or prognostic significance.

Objective: Our objective was to evaluate the association of serum biomarkers with baseline psoriatic arthritis (PsA) disease activity, pharmacodynamic effects of deucravacitinib on biomarker levels, and the relationship between biomarkers and clinical responses to deucravacitinib., Methods: The phase 2 trial (ClinicalTrials.gov identifier: NCT03881059) randomly assigned 203 patients with PsA 1:1:1 to placebo, deucravacitinib at 6 mg once daily (QD), or deucravacitinib at 12 mg QD. Serum biomarkers associated with the interleukin 23 (IL-23) pathway (IL-17A, β-defensin [BD-2], and IL-19), type I interferon pathway, inflammation, and collagen matrix turnover were measured by immunoassay. Clinical responses (≥75% improvement from baseline in the Psoriasis Area and Severity Index [PASI75] and ≥20% improvement from baseline in American College of Rheumatology criteria [ACR20] responses) were measured at week 16. Hematologic variables were also assessed., Results: IL-17A, BD-2, and IL-19 had a modest association with PASI scores (r = 0.4, r = 0.56, and r = 0.5, respectively) at baseline. In deucravacitinib groups, IL-17A, BD-2, IL-19, C-X-C motif ligand 9 (CXCL9), CXCL10, C-reactive protein, matrix metalloproteinase 3, and collagen type 4 degradation marker levels were significantly reduced at week 16 versus baseline (P < 0.01); higher levels of IL-23 pathway-associated biomarkers predicted higher PASI75 and ACR20 response rates in deucravacitinib-treated patients. Significantly higher PASI75 response rates were seen in patients with high baseline IL-17A (odds ratio 15.76) and BD-2 levels (odds ratio 15.41) versus low baseline IL-17A and BD-2 levels. Changes in hematologic variables that are characteristic of JAK inhibition were not observed with deucravacitinib., Conclusion: Deucravacitinib significantly impacted biomarkers associated with Tyk2 signaling pathways of key inflammatory cytokines, including IL-23 and type I interferon, and those related to collagen matrix turnover. These biomarkers may predict treatment responses to deucravacitinib., (© 2024 The Author(s). Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background: Acute mountain sickness (AMS) is the most prevalent condition resulting from hypobaric hypoxia (HH) at high altitudes. Although evidence suggests the involvement of inflammatory cytokines in AMS development, there is currently a lack of reports on variations in cytokine levels between individuals susceptible to AMS and those resistant to AMS prior to ascending to high altitude. Thus our current study aims to assess the predictive capability for AMS occurrence by evaluating differences in cytokine levels at low altitudes., Methods: The present study recruited 48 participants, who ascended from low altitude to middle high-altitude (3700 m) and further to extreme high-altitude (5000 m). Based on Lake Louise Score (LLS) at the two high altitudes, participants were categorized into severe AMS-susceptible (sAMS), moderate AMS-susceptible (mAMS), and non-AMS groups. The Bio-Plex MAGPIX System was employed to measure plasma levels of 11 inflammatory cytokines. Cytokines at low altitude and middle high-altitude were analyzed through receiver operating characteristic (ROC) analysis to obtain area under the ROC curve (AUROC), sensitivity, and specificity., Results: Based on LLS at 3700 m, we initially categorized the study subjects into the sAMS group (n = 8) and the Non-AMS group (n = 40). Among individuals in the non-AMS group (n = 40) at the altitude of 3700 m, those who developed AMS at the altitude of 5000 m were assigned to the mAMS group (n = 17), whereas those who did not experience AMS were included into the non-AMS group (n = 23). The concentration of TNF-α at low altitude exhibited robust predictive performance for predicting AMS occurrence at the altitude of 3700 m. Among the non-AMS group at the altitude of 3700 m, we identified that the concentration of IL-2 and IL-17A demonstrated high efficacy in predicting the onset of AMS following ascent to 5000 m. In addition, differentially expressed cytokines including IL-17A, TNF-α and IL-2 at low altitude possessed discriminatory potential among the three groups at 5000 m.., Conclusion: We posited that the levels of TNF-α, IL-2, IL-17A in serum of low altitude could be considered as potential biomarkers to predict the occurrence of AMS at high altitude., New & Noteworthy: Through the two comparisons at different two altitudes (baseline level and 3700 m), we provided a model to progressively screen individuals who are susceptible and resistant to different high altitudes (3700 m and 5000 m). TNF-α could firstly screen out the AMS susceptible individuals at the altitude of 3700 m. And through its combination with IL-2 and IL-17A, we could further screen out AMS susceptible individuals at the altitude of 5000 m., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Aortic endothelial diastolic dysfunction is an early complication of diabetes and the abnormal differentiation of Th17 cells is involved in the development of diabetes. However, the exact role of exercise on regulating the Th17 cells differentiation and the underlying molecular mechanisms remain to be elucidated in diabetic mice., Methods: db/db and db/m + mice were randomly divided into exercise and sedentary groups. Mice in exercise group were exercised daily, 6 days/week, for 6 weeks and mice in sedentary groups were placed on a nonmoving treadmill for 6 weeks. Vascular endothelial function was measured via wire myograph and the frequencies of Th17 from peripheral blood in mice were assessed via flow cytometry., Results: Our data showed that exercise improved insulin resistance and aortic endothelial diastolic function in db/db mice. In addition, the proportion of Th17 cells and IL-17A level in peripheral blood of db/db mice were significantly increased, and exercise could promote Th17 cell differentiation and reduce IL-17A level. More importantly, STAT3 or ROR-γt inhibitors could promote Th17 cell differentiation in db/db mice, while exercise significantly down-regulated p-STAT3/ROR-γt signaling in db/db mice, suggesting that exercise regulated Th17 differentiation through STAT3/ROR-γt signaling., Conclusions: This study demonstrated that exercise improved vascular endothelial function in diabetic mice via reducing Th17 cell differentiation through p-STAT3/ROR-γt pathway, suggesting exercise may be an important non-pharmacological intervention strategy for the treatment of diabetes-related vascular complications.

Background: Lung adenocarcinoma (LUAD) is the most common type of lung cancer, and its pathogenesis remains not fully elucidated. Inflammation and metabolic dysregulation are considered to play crucial roles in LUAD development, but their causal relationships and specific mechanisms remain unclear., Methods: This study employed a two-sample Mendelian randomization (MR) approach to systematically evaluate the causal associations between 91 circulating inflammatory factors, 1,400 serum metabolites, and LUAD. We utilized LUAD genome-wide association studies (GWAS) data from the FinnGen biobank and GWAS data of metabolites and inflammatory factors from the GWAS catalog to conduct two-sample MR analyses. For the identified key metabolites, we further used mediator MR to investigate their mediating effects in the influence of IL-17A on LUAD and explored potential mechanisms through protein-protein interaction and functional enrichment analyses., Results: The MR analyses revealed that IL-17A (OR 0.78, 95%CI 0.62-0.99) was negatively associated with LUAD, while 71 metabolites were significantly associated with LUAD. Among them, ferulic acid 4-sulfate may play a crucial mediating role in the suppression of LUAD by IL-17A (OR 0.87, 95%CI 0.78-0.97). IL-17A may exert its anti-LUAD effects through extensive interactions with genes related to ferulic acid 4-sulfate metabolism (such as SULT1A1, CYP1A1, etc.), inhibiting oxidative stress and inflammatory responses, as well as downstream tumor-related pathways of ferulic acid 4-sulfate (such as MAPK, NF-κB, etc.)., Conclusion: This study discovered causal associations between IL-17A, multiple serum metabolites, and LUAD occurrence, revealing the key role of inflammatory and metabolic dysregulation in LUAD pathogenesis. Our findings provide new evidence-based medical support for specific inflammatory factors and metabolites as early predictive and risk assessment biomarkers for LUAD, offering important clues for subsequent mechanistic studies and precision medicine applications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ding, Chen, Li and Ji.)

The IgG response against SARS-CoV-2 infection can persist for over six months (long response; LR). However, among 30% of those infected, the duration can be as short as three months or less (short response; SR). The present study assembled serological data on the anti-SARS-CoV-2 IgG response duration of two previous studies and integrated these results with the plasmatic cytokine levels and genetic profile of 10 immune-relevant SNPs that were also previously published, along with the plasmatic total IgG, IgA, and IgM levels, allowing for the genetic, clinical, immunological, and epidemiological aspects of the post-COVID-19 IgG response duration to be understood. The SR was associated with previous mild acute COVID-19 and with an SNP (rs2228145) in IL6R related to low gene expression. Additionally, among the SR subgroup, no statistically significant Spearman correlations were observed between the plasma levels of IL-17A and the Th17 regulatory cytokines IFN-γ (rs = 0.2399; p = 0.1043), IL-4 (rs = 0.0273; p = 0.8554), and IL-2 (rs = 0.2204; p = 0.1365), while among the LR subgroup, weaker but statistically significant Spearman correlations were observed between the plasma levels of IL-17A and IFN-γ (rs = 0.3873; p = 0.0016), IL-4 (rs = 0.2671; p = 0.0328), and IL-2 (rs = 0.3959; p = 0.0012). These results suggest that the Th17 response mediated by the IL-6 pathway has a role in the prolonged IgG response to SARS-CoV-2 infection.

Objective: This study aimed to evaluate inflammatory biomarkers in patients undergoing peritoneal dialysis and investigate their association with all-cause mortality or transfer to hemodialysis., Methods: This prospective cohort study included 43 patients undergoing peritoneal dialysis. Plasma levels of cytokines were measured using flow cytometry and capture enzyme-linked immunosorbent assay. Biomarkers were categorized based on their respective median values. Survival analysis was conducted using the Kaplan-Meier estimator, considering two outcomes: all-cause mortality and transfer to hemodialysis., Results: After adjusting for confounding factors, plasma levels above the median of the levels of CCL2 and plasma, as well as below the median of TNF-α, and the median of dialysate IL-17 levels, were associated with an increased risk of experiencing the specified outcomes after approximately 16 months of follow-up., Conclusion: These findings suggest that inflammatory biomarkers may be a valuable tool for predicting all-cause mortality and transfer to hemodialysis in patients undergoing peritoneal dialysis.

Background: The purpose of this study was to investigate the diagnostic value of IL-17 detection in bronchoalveolar lavage fluid (BALF) and plasma samples from nonneutropenic patients with invasive pulmonary aspergillosis., Methods: We retrospectively collected data on non-neutropenic patients who were suspected to have IPA admitted to the Third Affiliated Hospital of Soochow University between March 2020 to January 2023. IL-17 and GM were measured using enzyme-linked immunosorbent assays., Results: A total of 281 patients were enrolled in this study, of which 62 had proven or probable IPA and the remaining 219 patients were controls. The plasma and BALF IL-17 levels were significantly higher in the IPA group compared with the control group. The plasma GM, plasma IL17, BALF GM, and BALF IL17 assays had sensitivities of 56.5%, 72.6%, 68.7%, and 81.2%, respectively, and specificities of 87.7%, 69.4%, 91.9%, and 72.6%, respectively. The sensitivity of IL17 in plasma and BALF was higher than that of GM. Plasma GM in combination with IL-17 increases the sensitivity but does not decrease the diagnostic specificity of GM testing. The diagnostic sensitivity and specificity of BALF GM combined with IL-17 for IPA in non-neutropenic patients were greater than 80% and there was a significant increase in sensitivity compared with BALF GM., Conclusions: Plasma and BALF IL-17 levels were significantly higher in non-neutropenic patients with IPA. The sensitivity of plasma and BLAF IL-17 for diagnosing IPA in non-neutropenic patients was superior to that of GM. Combined detection of lavage fluid GM and IL17 significantly improves the diagnosis of IPA in non-neutropenic patients. The combined detection of GM and IL-17 in plasma also contributes to the diagnosis of IPA in patients who cannot tolerate invasive procedures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 He, Cao, Zhang and Feng.)

Purpose: To investigate the effect of dual-wavelength laser combined with bioceramics material iRoot SP on molar root canal treatment., Methods: A total of 104 patients receiving root canal treatment from January 2020 to June 2023 were selected and divided into control group and experimental group according to random number table method, with 52 cases in each group. The control group was treated with iRoot SP paste, and the experimental group was treated with dual-wavelength laser(Nd:YAG and Er:YAG) combined with iRoot SP paste. The total effective rate, pain degree and complications were compared. Serum interleukin-6 (IL-6), interleukin-17(IL-17), tumor necrosis factor-α(TNF-α), bleeding index(BI), depth of periodontal probing(PD) and clinical attachment level(CAL) were observed before treatment, 6 weeks and 12 weeks after treatment. SPSS 22.0 software package was used for statistical analysis., Results: The total effective rate of the experimental group was significantly higher than that of the control group, and the pain degree after root canal filling was significantly lower than the control group(P＜0.05). The levels of IL-6, IL-17, TNF-α, BI, PD and CAL in the experimental group were significantly lower than those in the control group at 6 and 12 weeks after treatment (P＜0.05)., Conclusions: Dual wavelength laser combined with bioceramic material iRoot SP has a better effect in the treatment of molar root canal, which is conducive to reducing periodontal inflammation and pain.

Primary membranous nephropathy (PMN), an autoimmune disease, is the most common cause of nephrotic syndrome in middle-aged non-diabetic adults. PMN pathophysiology includes Th1/Th2 paradigm. The IL-23/IL-17 pathway is implicated in autoimmune kidney disorders, but no study has examined its relationship with PMN. In several unrelated studies, PMN patients reported to have paradoxical IL-17 levels. This manuscript describes the best possible association of IL-23/IL-17 axis with PMN. Biopsy-proven PMN patients and age, gender-matched healthy controls were enrolled. Serum-PLA2R (Euroimmune, Germany), IL-23 and IL-17 (R&D; USA), was measured using ELISA along with biochemical parameters. Appropriate statistical tools were used for analysis. One hundred eighty-nine PMN patients (mean age 41.70 ± 12.53 years) and 100 controls (mean age 43.92 ± 10.93 years) were identified. One hundred forty were PLA2R-related. PMN patients had median proteinuria, serum albumin, and creatinine of 6.12 (3.875, 9.23) g/day, 2.32 (1.96, 2.9) g/dl, and 0.89 (0.7, 1.1) mg/dl, respectively. IL-17, but not IL-23, was significantly increased in PMN patients compared to controls (IL-17, median: 12.07 pg/ml (9.75, 24.56) vs median: 9.75 pg/ml (8.23, 17.03) p = 0.0002); (IL23, median: 6.04 pg/ml (4.22, 10.82) vs median: 5.46 pg/ml (3.34, 9.96) p = 0.142). IL-17 and IL-23 correlated significantly (p 0.05) in PMN patients, and similar trend was seen when grouped into PLA2R-related and -unrelated groups. The levels of IL-23 (p = 0.057) and IL-17 (p = 0.004) were high in MN patients that did not respond to the treatment. The current finding may indicate or suggest the involvement of IL-23/IL-17 PMN pathogenesis. A comprehensive investigation is needed to evaluate IL-23/IL-17 axis with renal infiltrating immune cells, and external stimuli., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Gene expression can provide distinct information compared to clinical biomarkers in the context of longitudinal clinical outcomes in asthma patients., Objective: This study examined the association between the gene expression levels of upstream (IL-25, IL-33, and TSLP) and downstream cytokines (IL-5, IL-4, and IL-13) in the T2 inflammatory pathway with a 12-month follow-up of exacerbation, lung function, and steroid use., Methods: Transcriptomic sequencing analysis was performed on peripheral blood mononuclear cells from 279 adult asthmatics. Survival analysis and linear mixed-effect models were used to investigate potential differences between the high-level and low-level gene expression groups and the clinical outcomes. Analysis was performed separately for the upstream, downstream, and all 6 cytokines., Results: In general, T2 inflammatory cytokine gene expression showed a weak correlation with blood eosinophil counts (all r < 0.1) and clinical outcomes. Among moderate-to-severe eosinophilic asthma (MSEA) patients, individuals with elevated levels of downstream cytokines were at increased risk of time-to-first exacerbation (p = 0.044) and a greater increase of inhaled corticosteroid use over time (p = 0.002) compared to those with lower gene expression. There was no association between baseline T2 inflammatory cytokine gene expression and the longitudinal changes in lung function over time among MSEA patients., Conclusion: These findings suggest that, among MSEA patients, the gene expression levels of downstream cytokines in the T2 inflammatory pathway may serve as indicators for endotyping asthma., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: To investigate the bidirectional influence between periodontitis and psoriasis, using the respective experimental models of ligature- and imiquimod-induced diseases on murine models., Materials and Methods: Thirty-two C57/BL6J mice were randomly allocated to four experimental groups: control (P- Pso-), ligature-induced periodontitis (P+ Pso-), imiquimod-induced psoriasis (P- Pso+) and periodontitis and psoriasis (P+ Pso+). Samples (maxilla, dorsal skin and blood) were harvested immediately after death. Measures of periodontitis (distance between the cemento-enamel junction and alveolar bone crest [CEJ-ABC] and the number of osteoclasts) and psoriasis (epidermal thickness and infiltrate cell [/0.03mm 2 ]) severity as well as systemic inflammation (IL-6, IL-17A, TNF-α) were collected., Results: The P+ Pso+ group exhibited the most severe experimental periodontitis and psoriasis, with the highest values of CEJ-ABC, number of osteoclasts, epidermal thickness and infiltrate cells in the dorsal skin, as well as the highest blood cytokine concentration. The P+ Pso- group presented with higher cell infiltrate (/0.03mm 2 ) compared to the control group (p <.05), while the P- Pso+ group showed substantially higher alveolar bone loss (CEJ-ABC) than the control group (p <.05)., Conclusions: Experimental periodontitis may initiate and maintain psoriasiform skin inflammation and, vice versa, experimental psoriasis may contribute to the onset of periodontitis. In a combined model of the diseases, we propose a bidirectional association between periodontitis and psoriasis via systemic inflammation., (© 2024 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Objective: To investigate the relationship between the severity and morphology of heterotopic ossification in the spinal ligaments including sacroiliac (SI) joints, and serum interleukin-17 (IL-17) levels in patients with ossification of the posterior longitudinal ligament (OPLL) with or without diffuse idiopathic skeletal hyperostosis (DISH), as well as a non-OPLL group., Methods: A total of 103 patients with OPLL [DISH (-), n = 50; DISH (+), n = 53] and 53 age- and gender-matched controls were included. The serum levels of IL-17 were analysed, and the severity of ectopic ossification and the morphology of ectopic bone formation were evaluated. The SI joint morphological variations were categorized into four types., Results: No significant differences were found in serum IL-17 levels between the OPLL and control groups. However, the DISH (+) group showed higher IL-17 levels than the DISH (-) group, especially in female patients (P = 0.003). Additionally, IL-17 levels were positively correlated with the number of flat vertebral units, this being one of the characteristic DISH ossification types (R2 = 0.199, P = 0.012). IL-17 levels in the type showing bridging osteophyte and bone fusion were significantly higher in the DISH (+) group than in the DISH (-) group., Conclusion: The morphological characteristics of paravertebral bone formation in the entire spine, including the SI joint, are likely associated with serum IL-17 levels in OPLL. These findings provide pathological and serological evidence of local inflammation contributing to paravertebral ossification of OPLL patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: The objective of this study was to investigate the impact of 92 inflammatory proteins on the risk of cardiovascular disease (CVD) in patients with early rheumatoid arthritis (RA)., Methods: This study included consecutive patients with early RA recruited between 1995 and 2002. Stored plasma samples were analyzed for 92 inflammatory proteins. CVD diagnoses were retrieved from national in-patient and cause-of-death registries. Statistical analyses were predesignated as hypothesis-driven or exploratory. For the latter, proteins were selected based on principal component analysis (ie, factor loading > 0.5 within main components). Potential predictors of CVD and coronary artery disease (CAD) were assessed using Cox regression., Results: Data on baseline levels of proteins and CVD were available for 163 patients. As hypothesized, levels of interleukin 17A (IL-17A) were associated with CVD (hazard ratio 1.35, 95% CI 1.02-1.78, adjusted for age, sex, hypertension, diabetes, smoking, and erythrocyte sedimentation rate [ESR]), although not significantly with CAD. Osteoprotegerin (OPG) levels were significantly associated with both outcomes, but only in crude models. No associations were observed for IL-6, tumor necrosis factor, monocyte chemotactic protein-1, or IL-8. In the exploratory analyses, MCP-3 in particular had significant associations with both outcomes in crude models., Conclusion: Circulating IL-17A at RA diagnosis predicted future CVD, although we cannot exclude the possibility that this finding is due to multiple testing. The association was independent of traditional CVD risk factors, and of ESR at the time of diagnosis. Further, OPG may be a predictor of CVD. We also identified some novel potential biomarkers for CVD in RA., (Copyright © 2024 by the Journal of Rheumatology.)

To analyze the role of interleukin IL-17A and IL-10 polymorphisms in susceptibility to juvenile idiopathic arthritis (JIA), 98 Finnish children and adolescents with JIA were studied. Data from the 1000 Genomes Project, consisting of 99 healthy Finns, served as the controls. The patients were analyzed for four IL-17A and three IL-10 gene-promoter polymorphisms, and the serum IL-17A, IL-17F, IL-10, and IL-6 levels were determined. The IL-17A rs8193036 variant genotypes (CT/CC) were more common among the patients than controls, especially in those with polyarthritis (OR 1.93, 95% CI 1.11-3.36; p = 0.020). IL-17A rs2275913 minor allele A was more common in patients (OR 1.45, 95% Cl 1.08-1.94; p = 0.014) and especially among patients with oligoarthritis and polyarthritis than the controls (OR 1.61, 95%CI 1.06-2.43; p = 0.024). Carriers of the IL-17A rs4711998 variant genotype (AG/AA) had higher serum IL-17A levels than those with genotype GG. However, carriers of the variant genotypes of IL-17A rs9395767 and rs4711998 appeared to have higher IL-17F levels than those carrying wildtype. IL-10 rs1800896 variant genotypes (TC/CC) were more abundant in patients than in the controls (OR 1.97, 95%CI 1.06-3.70; p = 0.042). Carriers of the IL-10 rs1800896 variant genotypes had lower serum levels of IL-17F than those with wildtype. These data provide preliminary evidence of the roles of IL-17 and IL-10 in the pathogenesis of JIA and its subtypes in the Finnish population. However, the results should be interpreted with caution, as the number of subjects included in this study was limited.

In recent times, the pathogenesis of generalized anxiety disorder (GAD) and the influence of pro- and anti-inflammatory cytokines on it have garnered considerable interest. Cytokine research, especially Th-17 cytokine research on GAD patients, is limited. Here, we aim to assess the role of interleukin-17A (IL-17A) and interleukin-23A (IL-23A) in the pathophysiology and development of GAD. This investigation included 50 GAD patients and 38 age-sex-matched healthy controls (HCs). A psychiatrist diagnosed patients with GAD and assessed symptom severity using the DSM-5 and the GAD-7 scales. The serum concentrations of IL-17A and IL-23A were determined using commercially available ELISA kits. GAD patients exhibited elevated levels of IL-17A (77.14 ± 58.30 pg/ml) and IL-23A (644.90 ± 296.70 pg/ml) compared to HCs (43.50 ± 25.54 pg/ml and 334.40 ± 176.0 pg/ml). We observed a positive correlation between disease severity and cytokine changes (IL-23A: r = 0.359, p = 0.039; IL-17A: r = 0.397, p = 0.032). These findings indicate that IL-17A and IL-23A may be associated with the pathophysiology of GAD. ROC analysis revealed moderately higher AUC values (IL-23A: 0.824 and IL-17A: 0.710), demonstrating their potential to discriminate between patients and HCs. Also, the sensitivity values of both cytokines were relatively higher (IL-23A: 80.49% and IL-17A: 77.27%). According to the present findings, there may be an association between peripheral serum levels of IL-17A and IL-23A and the pathophysiology and development of GAD. These altered serum IL-17A and IL-23A levels may play a role in directing the early risk of developing GAD. We recommend further research to ascertain their exact role in the pathophysiology and their performance as risk assessment markers of GAD., (© 2024. The Author(s).)

The incidence of hyperlipidemic acute pancreatitis (HLAP) has been increasing annually. However, it is unclear whether there is a correlation between serum inflammatory factors and HLAP. This study aimed to explore the relationship between serum inflammatory factors and HLAP., Methods: In this study, sixty patients with hyperlipidemic severe acute pancreatitis were registered from January 2020 to December 2024 at our hospital. Sixty healthy volunteers who underwent physical examination at the hospital physical examination center during the same period were selected as controls. Th1/Th2 cells, high-sensitivity C-reactive protein (hs-CRP), interleukin-17 (IL-17), tumor necrosis factor-alpha (TNF-α) were compared between two groups., Results: The BMI level of the HLAP group was higher than that of the control group. The levels of hs-CRP, IL-17, and TNF-α in the HLAP group were higher than those in the control group., Conclusion: High BMI, hs-CRP, IL-17, and TNF-α levels may be risk factors for HLAP.

Candida species are a normal human flora in humans' digestive and reproductive systems, oral cavity, skin, and mucosal surfaces. This study aimed to detect the immunological role of Candida infection by using some immunological markers. The results of levels in serum showed high concentrations of IgA (56.20 ± 12 pg/ml,29.55 ± 4.5 pg/ml respectively) and IgG (12.05 ± 3.218 pg/ml, 3.836 ± 1.23 pg/ml respectively) in mice infected with C. albicans and mice treated with Cefoperazone and infected with Candida with significant differences (P value < 0.05). The results showed high serum levels of IL-17(191.5 ± 42.81 pg/ml) and TLR2(7.651 ± 1.5 pg/ml) in group mice infected with C. albicans compared with negative control and group mice treated with Cefoperazone. Also, high levels of IL-17 (91.33 ± 4.816 pg/ml) and TLR2 (2.630 ± 0.5 pg/ml) in group mice treated with Cefoperazone and infected with Candida compared with negative control and group mice treated with Cefoperazone (P value < 0.05). The results of antibodies and immunological markers in the intestine showed high levels of IgA and IgG in mice infected with C.albicans (55.7 ± 4.9 pg/ml, 18.19 ± 0.63 pg/ml respectively).Also,IgA and IgG in mice treated with Cefoperazone and infected with Candida were high level (43.04 ± 2.1 pg/ml, 2.927 ± 0.2 pg/ml respectively) in mice infected with C. albicans with significant differences (P value < 0.05). The results levels of IL-17 and TLR2 were increased in mice infected with C. albicans (191.5 ± 42.81 pg/ml, 7.651 ± 1.5 pg/ml respectively) and mice treated with Cefoperazone and infected with Candida (91.33 ± 4.816 pg/ml,2.630 ± 0.5 pg/ml respectively) with significant differences (P < 0.05). In conclusion, this study demonstrated that cefoperazone treatment and infection by Candida albicans changed the microbiome components in the gut and finally can change host immune responses. It was observed that elevated levels of the antibodies production (IgA and IgG) and immunological markers (IL-17, and TLR2) in serum and the gut., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Atyaf Saied Hamied reports no administrative support, article publishing charges, equipment, drugs, or supplies, statistical analysis, travel, and writing assistance were provided by University of Baghdad. Atyaf Saied Hamied reports a relationship with University of Baghdad that includes: non-financial support. non If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Interleukin (IL)-17A contributes to hypertension in preclinical models. T helper 17 and dendritic cells are activated by NaCl, which could involve the epithelial Na + channel (ENaC). We hypothesized that the ENaC blocker amiloride reduces plasma IL-17A and related cytokines in patients with hypertension. Concentrations of IL-17A, IFN-γ, TNF, IL-6, IL-1β, and IL-10 were determined by immunoassays in plasma from two patient cohorts before and after amiloride treatment: 1 ) patients with type 2 diabetes mellitus (T2DM) and treatment-resistant hypertension ( n = 69, amiloride 5-10 mg/day for 8 wk) and 2 ) patients with hypertension and type 1 diabetes mellitus (T1DM) ( n = 29) on standardized salt intake (amiloride 20-40 mg/day, 2 days). Plasma and tissue from ANG II-hypertensive mice with T1DM treated with amiloride (2 mg/kg/day, 4 days) were analyzed. The effect of amiloride and benzamil on macrophage cytokines was determined in vitro. Plasma cytokines showed higher concentrations (IL-17A ∼40-fold) in patients with T2DM compared with T1DM. In patients with T2DM, amiloride had no effect on IL-17A but lowered TNF and IL-6. In patients with T1DM, amiloride had no effect on IL-17A but increased TNF. In both cohorts, blood pressure decline and plasma K + increase did not relate to plasma cytokine changes. In mice, amiloride exerted no effect on IL-17A in the plasma, kidney, aorta, or left cardiac ventricle but increased TNF in cardiac and kidney tissues. In lipopolysaccharide-stimulated human THP-1 macrophages, amiloride and benzamil (from 1 nmol/L) decreased TNF, IL-6, IL-10, and IL-1β. In conclusion, inhibition of ENaC by amiloride reduces proinflammatory cytokines TNF and IL-6 but not IL-17A in patients with T2DM, potentially by a direct action on macrophages. NEW & NOTEWORTHY ENaC activity may contribute to macrophage-derived cytokine release, since amiloride exerts anti-inflammatory effects by suppression of TNF and IL-6 cytokines in patients with resistant hypertension and type 2 diabetes and in THP-1-derived macrophages in vitro.

Objectives: To quantify associations of serum alarmins with risk of rheumatoid arthritis-associated interstitial lung disease (RA-ILD)., Methods: Using serum collected at enrolment, three alarmins (IL-33, thymic stromal lymphopoietin [TSLP] and IL-25) were measured in a multicentre prospective RA cohort. ILD was classified using systematic medical record review. Cross-sectional associations of log-transformed (IL-33, TSLP) or quartile (IL-25) values with RA-ILD at enrolment (prevalent RA-ILD) were examined using logistic regression, while associations with incident RA-ILD developing after enrolment were examined using Cox proportional hazards. Covariates in multivariate models included age, sex, race, smoking status, RA disease activity score and anti-cyclic citrullinated antibody positivity., Results: Of 2835 study participants, 115 participants (4.1%) had prevalent RA-ILD at baseline and an additional 146 (5.1%) developed incident ILD. There were no associations between serum alarmin concentrations and prevalent ILD in unadjusted or adjusted logistic regression models. In contrast, there was a significant inverse association between IL-33 concentration and the risk of developing incident RA-ILD in unadjusted (hazard ratio [HR] 0.73 per log-fold increase; 95% CI: 0.57, 0.95; P = 0.018) and adjusted (HR 0.77; 95% CI: 0.59, 1.00; P = 0.047) models. No significant associations of TSLP or IL-25 with incident ILD were observed., Conclusion: In this study, we observed a significant inverse association between serum IL-33 concentration and the risk of developing incident RA-ILD, but no associations with prevalent ILD. Additional investigation is required to better understand the mechanisms driving this relationship and how serum alarmin IL-33 assessment might contribute to clinical risk stratification in patients with RA., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Mucosal-associated invariant T (MAIT) cells are essential in defending against infection. Sepsis is a systemic inflammatory response to infection and a leading cause of death. The relationship between the overall competency of the host immune response and disease severity is not fully elucidated. This study identified a higher proportion of circulating MAIT17 with expression of IL-17A and retinoic acid receptor-related orphan receptor γt in patients with sepsis. The proportion of MAIT17 was correlated with the severity of sepsis. Single-cell RNA-sequencing analysis revealed an enhanced expression of lactate dehydrogenase A (LDHA) in MAIT17 in patients with sepsis. Cell-culture experiments demonstrated that phosphoinositide 3-kinase-LDHA signaling was required for retinoic acid receptor-related orphan receptor γt expression in MAIT17. Finally, the elevated levels of plasma IL-18 promoted the differentiation of circulating MAIT17 cells in sepsis. In summary, this study reveals a new role of circulating MAIT17 in promoting sepsis severity and suggests the phosphoinositide 3-kinase-LDHA signaling as a driving force in MAIT17 responses., Competing Interests: Disclosure Statement None declared., (Copyright © 2024 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Cytokines are of utmost importance in both the physiological and pathological immune responses of the human body. This study utilized flow cytometry to measure the levels of plasma interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-5 (IL-5) and interleukin-17A (IL-17A) and established their reference intervals, aiming to provide data support for the diagnosis and treatment of clinical diseases., Methods: According to the inclusion and exclusion criteria, a total of 728 reference individuals were included in this study from January 2023 to June 2023. The Kolmogorov-Smirnov test was used to analyse the distributions of plasma IL-2, IL-4, IL-5 and IL-17A. The reference intervals of plasma IL-2, IL-4, IL-5 and IL-17A were established by the unilateral percentile method (95th percentile) based on the guidelines of C28-A 3 and WS/T 402-2012., Results: In this study, the levels of plasma IL-2, IL-4, IL-5 and IL-17A were nonnormally distributed. The concentrations of plasma IL-2, IL-4, IL-5 and IL-17A in healthy adults were not significantly different by sex or age (all P > 0.05). Therefore, all the reference individuals were combined into one group, and the reference intervals of plasma IL-2, IL-4, IL-5 and IL-17 were established by flow cytometry (IL-2 ≤ 10.25 pg/mL, IL-4 ≤ 9.87 pg/mL, IL-5 ≤ 3.36 pg/mL and IL-17A ≤ 9.46 pg/mL)., Conclusions: We first established the reference intervals of plasma IL-2, IL-4, IL-5 and IL-17A in healthy adults based on a single-center population in the Jiangsu region in eastern China, which will provide an important reference value for evaluating human immune status and the diagnosis and treatment of clinical diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Second People's Hospital of Lianyungang. Published by Elsevier Ltd.. All rights reserved.)

Obstructive sleep apnea (OSA) is a chronic inflammatory disease characterized by partial or complete upper airway obstruction during sleep. We aimed to evaluate serum/plasma levels of several cytokines (interleukin [IL]-6, IL-12, IL-17, IL-18, and IL-23) in a systematic review meta-analysis in both adults and children with OSA compared with controls. We conducted a comprehensive search of 4 digital databases (PubMed, Web of Science, Scopus, and Cochrane Library) up until October 19, 2023, without any limitations. For our meta-analysis, we used Review Manager, version 5.3, and displayed the data as the standardized mean difference (SMD) and 95% confidence interval (CI) to assess the correlation between cytokine levels and OSA. We utilized Comprehensive Meta-Analysis version 3.0 software to conduct bias analyses, meta-regression, and sensitivity analyses. From 1881 records, 84 articles were included in the systematic review and meta-analysis. In adults, the pooled SMDs for IL-6 level were 0.79 ( P value < 0.00001), for IL-17 level were 0.74 ( P value = 0.14), and for IL-18 level were 0.43 ( P value = 0.00002). In children, the pooled SMD for IL-6 was 1.10 ( P value < 0.00001), for IL-12 was 0.47 ( P value = 0.10), for IL-17 was 2.21 (a P value = 0.24), for IL-18 was 0.19 ( P value = 0.07), and for IL-23 was 2.46 ( P value < 0.0001). The subgroup analysis showed that the ethnicity, mean body mass index, and mean apnea-hypopnea index for IL-6 levels in adults and the ethnicity for IL-6 levels in children were effective factors in the pooled SMD. The findings of the trial sequential analysis revealed that adequate evidence has been obtained. The analysis of IL levels in adults and children with OSA compared with those without OSA revealed significant differences. In adults, IL-6 and IL-18 levels were significantly higher in the OSA group, while in children, only IL-6 and IL-23 levels were significantly elevated.

Multisystem inflammatory syndrome in children (MIS-C) shares several clinical and immunological features with Kawasaki Disease (KD) and pediatric hyperinflammation, but the immuno-phenotypic overlap among these clinical mimics is still incompletely understood. Here we analyzed serum samples from treatment-naïve patients with MIS-C (n = 31) and KD (n = 11), pediatric hyperinflammation (n = 13) and healthy controls (HC, n = 10) by proximity extension assay (PEA) to profile 184 blood biomarkers. Collectively, immunophenotypic overlap between MIS-C and hyperinflammation exceeds overlap with KD. Overexpression of IL-17A in MIS-C and KD could best separate these conditions from hyperinflammatory conditions, while those were hallmarked by overabundance of adenosin deaminase and IL-18. Depletion in serum TNF-related subfamily member 9 (TNFRSF9) and apoptosis inducing ligand (TRAIL) linked with cardiovascular manifestations and myocarditis in MIS-C. Altogether, our analysis highlights important differences in molecular marker signatures also across different MIS-C and KD cohorts and suggests several previously unidentified molecular associations in context of cardiovascular inflammation., Competing Interests: Declaration of competing interest CH has received honoraria (lecture fees) from Novartis; HW has received honoraria (lecture fees) from Novartis and Takeda, and travel support from Octapharma and CSL-Behring; DF received speaker fees/honoraria from Chugai-Roche, Novartis and SOBI as well as research support from Novartis, Pfizer and SOBI. CK has received consulting fees from Novartis and Swedish Orphan Biovitrum (SOBI) (< $10,000 each) and receives research support from Novartis (> $10,000). No other disclosures relevant to this article were reported., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Problem: Adenomyosis (AM) is associated with immune response and inflammation. However, the role of T cell subsets in AM development has not been thoroughly understood., Method of Study: Patients with focal or diffuse AM were recruited. Serum cytokines were quantified by enzyme-linked immunosorbent assay (ELISA). Different T cell subsets in the blood and ectopic endometrium were determined by flow cytometry., Results: Serum interleukin-6 (IL-6) and macrophage-colony-stimulating factor (GM-CSF) were increased in patients with focal or diffuse AM before focused ultrasound ablation surgery (FUAS), but not after FUAS. Compared with the healthy control, the frequencies of CD8 + interferon-gamma (IFN-γ)-expressing cytotoxic T lymphocytes (CTLs), interleukin-17A (IL-17A)-expressing Tc17 cells, CD4 + T helper 1 (Th1) cells, and GM-CSF-expressing T helper (ThGM) cells were up-regulated in the blood of patients with AM, especially those with diffuse AM. However, these changes were eradicated after FUAS. Meanwhile, the frequencies of these T cell subsets were positively correlated with the CA-125 level. Furthermore, these T cell subsets were also increased in ectopic endometrium., Conclusions: Our study delineates for the first time the presence of CTLs, Tc17 cells, Th1, and ThGM cells in the blood and ectopic endometrium in AM. The results imply that T cell response might impact AM development., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Rheumatoid Arthritis (RA) is a chronic, progressive autoimmune disease, involves an intimate relationship between immune cells and cytokines and results in decreased lifespans and higher mortality rates. The goal of the current study was to investigate the impact of MicroRNA (miRNA)146a and interleukin-17 (IL-17) as prognosis markers in RA patients. This case-control study included 120 RA patients who visited the Rheumatology unit at Al-Saddar Medical City in the governorate of Najaf, and 30 normal controls. Venous blood samples were collected from both patients and controls. Blood samples were used for measuring IL-17 levels using an enzyme linked immunosorbent assay (ELISA) testing, and miRNA146a by the reverse transcription polymerase chain reaction (RT-PCR). The results showed higher frequency of RA in women than in men with elevate incidence in patients aged 40-59 years and 1-2 years RA disease duration of. The level of IL-17 was significantly higher in serum of RA patients compared with the control group (p < 0.0001). IL-17 level was significantly increased among the patients in RA stage 4 (p < 0.0001). IL-17 level was significantly increased in patients without treatment compared with treated patients. The expression of miRNA-146a was significantly higher in the patients' group than control group. In conclusion, IL-17 may play critical role in chronic inflammation and can be used as diagnostic biomarker for RA. miRNA-146a is overexpressed in RA patient relative to healthy individuals and it acts as a negative regulator for IL-17., (Copyright© by the Egyptian Association of Immunologists.)

Objectives: To investigate the expression of microRNA-142 (miR-142) in children with autoimmune thyroid disease (AITD) and its relationship with the imbalance of helper T cell 17 (Th17) and regulatory T cell (Treg)., Methods: A total of 89 children hospitalized for AITD from January 2019 to December 2022 were prospectively selected as the study subjects, including 48 children with Graves' disease (GD group) and 41 children with Hashimoto's thyroiditis (HT group). Additionally, 55 healthy children undergoing physical examinations during the same period were selected as the control group. The differences in serum miR-142, antithyroglobulin antibody (TGAb), antithyroperoxidase antibody (TPOAb), Th17/Treg, and interleukin-17 (IL-17) expression were compared among the groups., Results: The expression of miR-142, TPOAb, TGAb, Th17, Th17/Treg, and IL-17 in the GD group and HT group was higher than that in the control group, while Treg was lower than that in the control group ( P <0.05). Pearson correlation analysis revealed that in the GD group, miR-142 was positively correlated with TPOAb, TGAb, Th17, Th17/Treg, and IL-17 ( r =0.711, 0.728, 0.785, 0.716, 0.709, respectively; P <0.001) and negatively correlated with Treg ( r =-0.725, P <0.001); in the HT group, miR-142 was positively correlated with TPOAb and TGAb ( r =0.752, 0.717, respectively; P <0.001)., Conclusions: miR-142 is highly expressed in children with AITD, and its expression may be related to the Th17/Treg imbalance in children with GD.

Objective: We assessed and compared immunologic differences and associations with clinical response to guselkumab, a fully human interleukin (IL)-23p19 subunit inhibitor, in participants with active psoriatic arthritis (PsA) who were biologic-naive or had inadequate response to tumor necrosis factor inhibitors (TNFi-IR)., Methods: Serum biomarker levels at baseline and after treatment with guselkumab 100 mg every 8 weeks were compared between biologic-naive (n = 251) and TNFi-IR (n = 93) subgroups identified in the pooled DISCOVER-1/DISCOVER-2/COSMOS data set. Baseline biomarker levels determined by achievement of week 24 clinical responses (≥75%/90% improvement in Psoriasis Area and Severity Index [PASI 75/90], Investigator's Global Assessment [IGA] of psoriasis score 0/1 and ≥2-point improvement], ≥20% improvement in American College of Rheumatology criteria [ACR20]) were compared between prior treatment subgroups., Results: Baseline IL-22, TNFα, and beta defensin-2 (BD-2) levels were significantly lower in biologic-naive than in TNFi-IR participants. With guselkumab, week 24 IL-17A, IL-17F, IL-22, serum amyloid A, C-reactive protein, IL-6, and BD-2 levels were significantly reduced from baseline in biologic-naive and TNFi-IR participants (≥1.4-fold difference, nominal P < 0.05). Clinical responders to guselkumab exhibited significantly higher baseline levels of several biomarkers than nonresponders (IL-17A, IL-17F, BD-2 in biologic-naive PASI 90 responders; IL-17A, BD-2 in TNFi-IR IGA 0/1 responders; IL-22, BD-2 in TNFi-IR PASI 90 responders [nominal P < 0.05]) and trended higher in TNFi-IR ACR20 responders., Conclusion: Guselkumab modulates IL-23 signaling and provides consistent pharmacodynamic effects in both biologic-naive and TNFi-IR PsA patients. Significantly elevated baseline IL-22, TNFα, and BD-2 levels and associations between baseline IL-22, IL-17A, and BD-2 levels and skin responses to guselkumab suggest greater dysregulation of IL-23/Th17 signaling in patients with TNFi-IR., (© 2024 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)