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Interleukin-10 (IL-10) is a key anti-inflammatory cytokine that can limit immune cell activation and cytokine production in innate immune cell types1. Loss of IL-10 signalling results in life-threatening inflammatory bowel disease in humans and mice-however, the exact mechanism by which IL-10 signalling subdues inflammation remains unclear2-5. Here we find that increased saturated very long chain (VLC) ceramides are critical for the heightened inflammatory gene expression that is a hallmark of IL-10 deficiency. Accordingly, genetic deletion of ceramide synthase 2 (encoded by Cers2), the enzyme responsible for VLC ceramide production, limited the exacerbated inflammatory gene expression programme associated with IL-10 deficiency both in vitro and in vivo. The accumulation of saturated VLC ceramides was regulated by a decrease in metabolic flux through the de novo mono-unsaturated fatty acid synthesis pathway. Restoring mono-unsaturated fatty acid availability to cells deficient in IL-10 signalling limited saturated VLC ceramide production and the associated inflammation. Mechanistically, we find that persistent inflammation mediated by VLC ceramides is largely dependent on sustained activity of REL, an immuno-modulatory transcription factor. Together, these data indicate that an IL-10-driven fatty acid desaturation programme rewires VLC ceramide accumulation and aberrant activation of REL. These studies support the idea that fatty acid homeostasis in innate immune cells serves as a key regulatory node to control pathologic inflammation and suggests that metabolic correction of VLC homeostasis could be an important strategy to normalize dysregulated inflammation caused by the absence of IL-10.

INTRODUCTION: Staphylococcus aureus bacteremia (SAB) is a life-threatening infection particularly involving methicillin-resistant S. aureus (MRSA). In contrast to resolving MRSA bacteremia (RB), persistent MRSA bacteremia (PB) blood cultures remain positive despite appropriate antibiotic treatment. Host immune responses distinguishing PB vs. RB outcomes are poorly understood. Here, integrated transcriptomic, IL-10 cytokine levels, and genomic analyses sought to identify signatures differentiating PB vs. RB outcomes. METHODS: Whole-blood transcriptomes of propensity-matched PB (n=28) versus RB (n=30) patients treated with vancomycin were compared in one independent training patient cohort. Gene expression (GE) modules were analyzed and prioritized relative to host IL-10 cytokine levels and DNA methyltransferase-3A (DNMT3A) genotype. RESULTS: Differential expression of T and B lymphocyte gene expression early in MRSA bacteremia discriminated RB from PB outcomes. Significant increases in effector T and B cell signaling pathways correlated with RB, lower IL-10 cytokine levels and DNMT3A heterozygous A/C genotype. Importantly, a second PB and RB patient cohort analyzed in a masked manner demonstrated high predictive accuracy of differential signatures. DISCUSSION: Collectively, the present findings indicate that human PB involves dysregulated immunity characterized by impaired T and B cell responses associated with excessive IL-10 expression in context of the DNMT3A A/A genotype. These findings reveal distinct immunologic programs in PB vs. RB outcomes, enable future studies to define mechanisms by which host and/or pathogen drive differential signatures and may accelerate prediction of PB outcomes. Such prognostic assessment of host risk could significantly enhance early anti-infective interventions to avert PB and improve patient outcomes.

BackgroundTobacco smoke exposure (TSE) has inflammatory and immunosuppressive effects which may be associated with altered levels of inflammatory markers and pediatric illnesses.ObjectiveThe primary objective was to examine the associations of cotinine-confirmed and parent-reported child TSE patterns and discharge diagnoses with C-reactive protein (CRP), IL-8, and IL-10 in 0-11-year-old pediatric emergency department (PED) patients who lived with ≥ 1 smoker.MethodsSaliva samples were obtained from 115 children with a mean (SD) age of 3.5 (3.1) years during the PED visit (T0). Saliva was analyzed for cotinine, CRP, IL-8, and IL-10. Parents self-reported their children's TSE patterns; children's medical records were reviewed to identify and categorize discharge diagnoses. Linear regression models were utilized to find T0 associations of cotinine-confirmed and parent-reported child TSE patterns, and PED diagnoses with each inflammatory marker. All models were adjusted for child race/ethnicity, child sex, annual household income, and housing type. The TSE models also adjusted for child discharge diagnosis.ResultsAt T0, the geometric mean (GeoM) of cotinine was 4.1 ng/ml [95 %CI = 3.2-5.2]; the GeoMs of CRP, IL-8, and IL-10 were 3,326 pg/ml [95 %CI = 2,696-4,105], 474 pg/ml [95 %CI = 386-583], and 1.1 pg/ml [95 %CI = 0.9-1.3], respectively. Parent-reported child TSE patterns were positively associated with ln-transformed CRP levels, while adjusting for the covariates (β^ = 0.012 [95 %CI:0.004-0.020], p = 0.037). In the parent-reported child TSE pattern model, there were significant positive associations between the covariate of child age with CRP and IL-8 levels (p = 0.028 and p

• Aberrant LHb hyperactivity drives susceptibility to depressive-like behaviors induced by maternal separation. • LHb IL-10 levels suppress neuronal activation and exert an anti-depressant effect. • IL-10 regulates the trafficking of LHb GABA A receptors and functions through PI3K/pAKT/gephyrin cascades. Maternal separation (MS), a form of early life adversity, increases the risk of psychiatric disorders in adulthood by intricately linking cytokines and mood-regulating brain circuits. The Lateral Habenula (LHb) encodes aversive experiences, contributes to negative moods, and is pivotal in depression development. However, the precise impact of MS on LHb cytokine signaling and synaptic plasticity remains unclear. We reported that adolescent MS offspring mice displayed susceptibility to depression behavioral phylotypes, with neuronal hyperactivity and an imbalance in pro-inflammatory and anti-inflammatory cytokines in the LHb. Moreover, the decreased IL-10 level negatively correlated with depressive-like behaviors in susceptible mice. Functionally, LHb IL-10 overexpression restored decreased levels of PI3K, phosphorylated AKT (pAKT), gephyrin, and membrane GABA A receptor proteins while reducing abnormally elevated GSK3β and Fos expression, rescuing the MS-induced depression. Conversely, LHb neuronal IL-10 receptor knockdown in naive mice increased Fos expression and elicited depression-like symptoms, potentially through impaired membrane GABA A receptor trafficking by suppressing the PI3K/pAKT/gephyrin cascades. Hence, this work establishes a mechanism by which MS promotes susceptibility to adolescent depression by impeding the critical role of IL-10 signaling on neuronal GABA A receptor function. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia is a complex neuropsychiatric disorder. Growing evidence indicates that the activation of the inflammatory response system with interleukin (IL)-2, IL-4, IL-8, IL-10, and tumor necrosis factor-alpha (TNF-α) plays an important role in the pathogenesis of schizophrenia,. However, clinical data on cytokine levels in patients with schizophrenia treated with antipsychotics are inconsistent or inconclusive. In this study, we have examined inflammatory factors' alterations and their relationship to changes in clinical symptoms before and after olanzapine treatment of drug-naive patients with first-episode schizophrenia. Methods: We recruited 142 hospitalized patients with first-episode schizophrenia as a study group; blood samples were collected, and the patients were assessed for clinical symptoms at baseline and after 6 weeks of olanzapine treatment. One hundred individuals with no history of mental illness were also recruited as healthy controls. Blood samples were collected, and the serum levels of IL-2, IL-4, IL-8, IL-10, and TNF-α were determined using an enzyme cycling assay. The severity of clinical symptoms was assessed according to the Positive and Negative Syndrome Scale (PANSS). Results: Individuals with schizophrenia had lower IL-8 levels and higher IL-10 levels than healthy controls (P < 0.001). Positive correlations were detected between serum IL-2 and IL-10 concentrations and each subscale of the PANSS (all P < 0.05). Moreover, a negative correlation existed between the serum IL-8 concentration and the PANSS negative score (r = − 0.172, P = 0.040). After 6 weeks of treatment, serum IL-8 levels in the patient group were lower than at baseline (P < 0.001), whereas serum IL-10 and TNF-α levels were higher than at baseline (all P < 0.05). Therefore, serum IL-10 can be determined as an independent risk factor for outcome in patients with first-episode schizophrenia (P = 0.02, OR = 2.327). Furthermore, serum IL-2, IL-10, and TNF-α levels were significantly lower, whereas the serum IL-8 level was significantly higher (P < 0.001) in the healthy control group than in the "response" and "no-response" treatment groups respectively. Conclusions: Our results indicate that serum IL-2, IL-8, IL-10, and TNF-α levels may be involved in the pathophysiological mechanisms of schizophrenia and correlate with the effects of olanzapine. [ABSTRACT FROM AUTHOR]

Introduction: Due to its remarkable anti-inflammatory pharmacological activity, Farfarae Flos has gained extensive usage in the treatment of various inflammatory diseases such as bronchitis, pneumonia, prostatitis and colitis. And Farfarae Flos come in two color types depending on the color of the flowers: yellowish-white (YW), and purplish-red (PR). However, the difference in anti-inflammatory activity and metabolic profiles between the two flower colors remains unexplored. Methods: This study aims to explore the difference in the anti-inflammatory potential between YW and PR variants of Farfarae Flos and unravel the mechanisms responsible for the observed differences in anti-inflammatory activity through an integrated approach encompassing untargeted metabolomics and in vivo/vitro experimental studies. Initially, we verified the contrasting effects of YW and PR on the inhibition of the inflammatory factors interleukin-6 (IL-6) and nitric oxide (NO) by utilizing an in vitro RAW 264.7 cell inflammation model. Subsequently, a comprehensive evaluation of the systemic inhibitory capacity of YW and PR on IL-6, Interleukin-10 (IL-10), and tumor necrosis factor-a (TNF-a) was conducted using a validated whole-body mouse model, followed by the analysis of inflammatory factors and histological examination of collected serum, liver, and spleen after 7 days. Furthermore, non-targeted metabolomics profiling was employed to analyze the metabolite profiles of Farfarae Flos with different colors, and quantitative analysis was conducted to identify differential metabolites between YW and PR. The correlation between the anti-inflammatory activities of differentially accumulated metabolites (DAMs) and Farfarae Flos was investigated, resulting in the identification of 48 compounds exhibiting significant anti-inflammatory activity. Additionally, KEGG pathway enrichment analysis was performed to elucidate the underlying mechanisms. Results: Our findings demonstrate that both YW and PR possess antiinflammatory abilities, with PR exhibiting significantly superior efficacy. The integration of in vivo/vitro experiments and non-targeted metabolomics confirmed the exceptional anti-inflammatory potential of PR and solidified its classification as the "purplish-red better" of Farfarae Flos. Discussion: This study provides valuable insights into the breeding and medical transformation of Farfarae Flos varieties, along with a scientific basis for the establishment of quality standards and the development of new drugs utilizing Farfarae Flos. [ABSTRACT FROM AUTHOR]

Objective: This case–control study aimed to investigate the diagnostic accuracy of salivary interleukin (IL)‐1β, IL‐10, and IL‐1β/IL‐10 ratio to discriminate periodontitis from periodontal health and stable from unstable periodontitis. Methods: Saliva samples were collected from 135 (healthy on an intact periodontium = 45 [as healthy control], stable periodontitis = 39, and unstable periodontitis = 51) participants, and then clinical periodontal parameters were recorded. An enzyme‐linked immunosorbent assay was used to determine salivary levels of IL‐1β and IL‐10. Area under the curves (AUCs), sensitivity, and specificity of IL‐1β, IL‐10, and IL‐1β/IL‐10 were estimated to discriminate between groups. Result: The level of salivary IL‐1β was significantly higher in unstable periodontitis than in stable periodontitis and healthy control groups (426 ± 59, 247 ± 55, and 204 ± 36 pg/ml [picograms per milliliter], respectively). While the level of salivary IL‐10 was significantly higher in the control group (360.7 ± 80.5 pg/ml) than unstable periodontitis group (146.92 ± 1.8 pg/ml), no significant difference was found between the control and stable periodontitis (317.04 ± 59.8 pg/ml) groups. IL‐1β, IL‐10, and IL‐1β/IL‐10 had significant diagnostic accuracy for differentiating healthy control from unstable periodontitis (AUCs = 0.99, 0.96, and 1; sensitivity = 0.98,1, and 1; specificity = 0.95, 0.95, and 1, respectively). Similarly, they showed significant diagnostic accuracy in distinguishing unstable from stable periodontitis (AUCs = 0.98, 0.99, and 1; sensitivity = 0.94, 1, and 1; specificity = 0.94, 0.97, and 1, respectively). Conclusion: Salivary IL‐1β, IL‐10, and IL‐1β/IL‐10 have a high potential to discriminate healthy control from periodontitis and stable from unstable periodontitis. Trial Registration: ClinicalTrials.gov identifier: NCT05722613 [ABSTRACT FROM AUTHOR]

Functional dyspepsia (FD) is known to be influenced by gut microbiota (GM) and circulating inflammatory proteins (CIPs), however, the causal relationship between GM, CIPs and FD haven't been investigated. This study employed two-sample Mendelian Randomization (TSMR) to investigate their associations using data from Genome-Wide Association Studies (GWAS). In this study, Inverse-variance weighted (IVW) method was employed as the primary analysis, with supplementary approaches including weighted median, weighted mode, simple mode, and MR-Egger. Heterogeneity and pleiotropy were assessed using the Cochrane Q test, MR-Egger intercept test, and MR-PRESSO global test. Totally, 196 GM traits and 91 CIPs were analyzed, and the results uncovered the causal impact of 12 GM taxa and 5 proteins on functional dyspepsia (FD). 9 GM genera were linked to a reduced risk of FD, while 3 GM genera were associated with an increased risk of FD.Additionally, reverse analysis revealed no FD-GM causation. Furthermore, IL-12, IL-10, CXCL10, CXCL9 and VEGFA were significantly correlated with FD, with CXCL9 and VEGFA acting as mediators in the association between GM traits and FD. Taken together, our findings established a link between specific GM and CIPs in the pathogenesis of FD, offering novel insights for its diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Cytokines operate in concert to maintain immune homeostasis and coordinate immune responses. In cases of ER+ breast cancer, peripheral immune cells exhibit altered responses to several cytokines, and these alterations are correlated strongly with patient outcomes. To develop a systems-level understanding of this dysregulation, we measured a panel of cytokine responses and receptor abundances in the peripheral blood of healthy controls and ER+ breast cancer patients across immune cell types. Using tensor factorization to model this multidimensional data, we found that breast cancer patients exhibited widespread alterations in response, including drastically reduced response to IL-10 and heightened basal levels of pSmad2/3 and pSTAT4. ER+ patients also featured upregulation of PD-L1, IL6Rα, and IL2Rα, among other receptors. Despite this, alterations in response to cytokines were not explained by changes in receptor abundances. Thus, tensor factorization helped to reveal a coordinated reprogramming of the immune system that was consistent across our cohort. [ABSTRACT FROM AUTHOR]

Early detection of COVID-19 improves the chance of recovery and helps identify high-risk patients. Our study aimed to statistically predict the time to improvement with the admission data of COVID-19 patients. Methods: Our prospective cohort study occurred between January and September 2022 at Alexandria University Hospital's outpatient clinic and isolation department. We enrolled 43 patients after assessing their eligibility and collecting their baseline data. Results: The mean age was 34.8 years (± 12.3). Most of them were females (65.1%). The mean of oxygen saturation was 95.2% (± 2.8). We used linear regression to predict how long it would take to improve [time to improvement (days) = 1.186*P (mmol/L) + 0.010*IL-10 (pg/mL)]. Its diagnostic performance was 0.723 (95% CI: 0.552–0.894), and it was accurate at predicting improvement within a week but not at longer delays; additionally, its positive and negative predictive values were 56.3% and 85.2%, respectively. Conclusion: We recommend monitoring phosphorus and interleukin-10 levels. The time-to-improvement delay negatively correlated with a reduction in baseline oxygen saturation upon admission. Additionally, for every 0.84 meq/L increase in phosphorus or 100 pg/mL increase in interleukin-10, there was a 1-day delay provided that the other was constant, with a coefficient of determination of 85.9%. [ABSTRACT FROM AUTHOR]

Background: Transient receptor potential vanilloid type 4 (TRPV4) is a versatile ion channel with diverse roles in immune cells, including macrophages. While its function in inflammation remains debated, we investigated its role in regulating IL-10 production and its impact on macrophage reprogramming during inflammation. Methods: We investigated the connection between TRPV4 activation and CREB-mediated IL-10 production during inflammation. Notably, this signaling pathway was found to reprogram macrophages and enhance their ability to resist inflammatory damage. The experiments were conducted on primary macrophages and were further corroborated by animal studies. Results: In response to TRPV4 activation during inflammation, we observed a significant increase in intracellular Ca2+ levels, which triggered the activation of the transcription factor CREB, subsequently upregulating IL-10 production. This IL-10 played a pivotal role in reprogramming macrophages to withstand inflammatory damage. Using a mouse model of acute lung injury (ALI), we confirmed that TRPV4 activation during ALI led to IL-10 secretion, but this increase did not significantly contribute to inflammation resolution. Moreover, we found that TRPV4 prevented the accumulation of dysfunctional mitochondria in macrophages through the CREB-IL-10 axis during inflammation. Suppression of CREB or TRPV4 inhibition exacerbated mitochondrial dysfunction, while treatment with recombinant IL-10 mitigated these effects. Additionally, IL-10 induced mitophagy and cleared dysfunctional mitochondria in LPS-exposed cells. Conclusion: Our study highlights the essential role of TRPV4 in regulating IL-10 production and mitochondrial health in macrophages during inflammation. These findings contribute to understand the role of TRPV4 in immune responses and suggest potential therapeutic targets for modulating inflammation-induced cellular dysfunction. [ABSTRACT FROM AUTHOR]

Ectoparasites Dactylogyrus spp. mainly infest fish gills and severely damage the host's gill tissues. Correspondingly, the explanation of the interaction of fish with Dactylogyrus spp. infection is still insufficient. The present study describes the changes in hemato-biochemical, immune, antioxidant, genotoxic, and pathological indices response of Nile tilapia (Oreochromis niloticus) severely (n > 50), mildly infected (n = 1–50), and uninfected with Dactylogyrus spp. Data showed the adverse effect of hemato-biochemical indices in infected fish compared to uninfected, notably in severely infected O. niloticus. Compared to uninfected fish, there is a significantly decreased serum lysozyme and complement C3 and increased IgM and phagocytic activity along with significant upregulation of (COX-2), (IL-1β), (TNF-α), and (IL-10) genes in infected fish partially, in severely infected fish. Concisely, indices of antioxidants in the liver and gills marked an increased level of MDA in the infected fish compared to the uninfected fish. Conversely, levels of SOD, CAT, and GSH were decreased significantly with damaged DNA in the gills and liver of infected groups, particularly in severely infected (P < 0.05). Histopathologically investigating livers and gills in infected Nile tilapia indicated damaging and degenerative alterations, particularly with severe infection. Findings showed that Dactylogyrus spp.–infected Nile tilapia were effective in improving our knowledge of fish-pathogen interactions, which may be essential for fish defense against parasite infection. [ABSTRACT FROM AUTHOR]

Purpose: Bariatric surgery poses an ever-increasing importance in the effective and long-lasting treatment of obesity, a condition strongly associated with inflammation and increased risk of other diseases and health problems. In obesity-related inflammation, maintaining a balance between pro-inflammatory and anti-inflammatory cytokines is crucial. In this study, we examined early effects of laparoscopic sleeve gastrectomy (LSG) on inflammatory and anti-inflammatory cytokines in obese patients, and assessed their effect on postoperative weight loss. Materials and Methods: This prospective cohort study was conducted from September 2022 till June 2023. Fifty obese adults were enrolled for LSG. All patients underwent assessments of body measurements, as well as levels of interleukin-6 (IL-6), interleukin-10 (IL-10), and TNF-alpha at baseline and 3 months postsurgery. We developed a decision tree model to predict the success of weight loss. Results: At 3 months postsurgery, patients lost 18.9 ± 6.9 kg of excess body weight. A significant decrease was observed for IL-10 (p < 0.0001), simultaneously with a significant increase in IL-6 (p < 0.0001). We found that high IL-6 (> 1.169 pg/mL) levels could contribute to an effective weight loss among patients with a baseline BMI less than 47.46 kg/m2. Conclusion: Study revealed that 3 months after bariatric surgery, inflammation persists, and its markers significantly influence postoperative weight loss, as indicated by BMI range. Distinct behaviors of IL-10 and IL-6 in relation to obesity underline the necessity of considering individual cytokine profiles when evaluating bariatric surgery outcomes. [ABSTRACT FROM AUTHOR]

PD-1 (programmed cell death protein-1)/PD-L1 (programmed cell death ligand 1) as well as IL-10 (interleukin-10)/IL-10R (interleukin-10 receptor) interactions play a major role in tumor immune evasion in various malignancies. Several studies investigated the expression of PD-1 on T lymphocytes in pleural effusions (PE) in patients with malignant diseases. However, results in malignant pleural effusions (MPE) compared to benign PE (BPE) are underreported. In this prospective study, 51 patients (median age 66 years, IQR 54–78, 47% male) with PE of malignant or benign origin at the Medical University of Vienna between March 2021 and November 2022 were enrolled and divided into three groups according to the cytological results (group 1: MPE [n = 24, 47%]; group 2: BPE in malignant disease [n = 22, 43%]; group 3: BPE in benign disease [n = 5, 10%]). In the cytological samples, T cells were analyzed for the expression of PD-1 and IL-10R via flow cytometry. In MPE, the proportion of PD-1+ T lymphocytes on CD4+ cells was significantly lower than in BPE (40.1 vs. 56.3 in group 1 vs. 3, p = 0.019). Moreover, a significantly lower expression of PD-1+ IL-10R+ CD8+ (9.6 vs. 35.2 in group 1 vs. 2, p = 0.016; 9.6 vs. 25.0 in group 1 vs. 3, p = 0.032) and a significantly higher expression of PD-1-IL-10R-CD8+ T lymphocytes (43.7 vs. 14.0 in group1 vs. 2, p = 0.045; 43.7 vs. 23.3 in group 1 vs. 3, p = 0.032) were observed in MPE when compared to BPE. The frequency of T cells expressing PD-1 and IL-10R on CD8+ T cells is significantly lower in MPE compared to BPE regardless of the underlying disease indicating a different microenvironment in PE driven by the presence of tumor cells. Our observation spotlights the possible involvement of PD-1 and IL-10R in MPE. [ABSTRACT FROM AUTHOR]

Objective: This study was to investigate the correlation between airway inflammation and lung function impairment in patients with bronchiectasis with different FEV, and to analyze the influencing factors of lung function impairment. Methods: 80 patients with bronchiectasis admitted to the respiratory department of our hospital from May 2022 to January 2024 were selected as research objects. General data of each group were analyzed, and lung function and airway inflammatory cytokine levels were compared in each group. Pearson linear analysis was used to analyze the relationship between lung function and airway inflammation in patients with bronchiectasis, and multi-factor Logisitic regression was used to analyze the influencing factors of lung function impairment in patients with bronchiectasis. Results: The FVC, FEV1/FVC and DLCO evaluation of the three groups were included in the study and the difference among the groups was compared. The results showed that the FVC, FEV1/FVC and FVC of the high FEV, group and the medium FEV, group were higher than those of the low FEV, group. FVC, FEV1/FVC and FVC in high FEV, group were higher than those in medium FEV, group (P<0.05). The levels of ESR, CRP, WBC, NEUT, PCT, IL-4, IL-6, IL-10 and TNF-a in the three groups were included in the study and the differences between the groups were compared. The levels of ESR, CRP, WBC, NEUT, PCT, IL-4, IL-6 and TNF-a in high and medium FEV, groups were lower than those in low FEV, group, and the levels of IL-10 were higher than those in low FEV₁ group (P<0.05). The levels of ESR, CRP, WBC, NEUT, PCT, IL-4, IL-6 and TNF-a in high FEV₁ group were lower than those in medium FEV₁ group, and the levels of IL-10 were higher than those in medium FEV, group(P<0.05). The results of Pearson linear analysis showed that FEV₁, FVC, FEV1/FVC and DLCO were positively correlated with airway inflammatory factors ESR, CRP, WBC, NEUT, PCT, IL-4, IL-6 and TNF-a, and negatively correlated with IL-10 in patients with bronchiectasis (P<0.05). Independent variables were set as the indicators with differences in comparison in the above data, including FVC, FEV1/FVC, DLCO, ESR, CRP, WBC, NEUT, PCT, IL-4, IL-6, IL-10, and TNF-a. The dependent variable was impaired lung function in patients with bronchiectasis. Multivariate Logisitic regression analysis was performed, and the results showed that The influential factors of impaired lung function in patients with bronchiectasis are FVC, FEV1/FVC, DLCO, ESR, CRP, WBC, NEUT, PCT, IL-4, IL-6, IL-10, TNF-α. Conclusion: Airway inflammation increases with the increase of FEV, level in patients with bronchiectasis, which is closely related to lung function and is an influential factor of lung function impairment. [ABSTRACT FROM AUTHOR]

SAPHO syndrome is a complex inflammatory disorder affecting the skin and bones, characterized by osteomyelitis, acne, and pustulosis. Cytokines play a pivotal role in the pathogenesis of SAPHO syndrome, especially in inflammatory responses and immune regulation. This article reviews the cytokines involved in the pathogenesis of SAPHO syndrome, such as tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), IL-6, IL-10, and transforming growth factor-β (TGF-β), and discusses their potential as intervention points for treatment. These findings elucidate the intricate immune regulatory network of SAPHO syndrome and provide a theoretical foundation for the development of new targeted therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Pulmonary fibrosis (PF) is an aging-related progressive lung disorder. The aged lung undergoes functional and structural changes termed immunosenescence and inflammaging, which facilitate the occurrence of fibrosis. Interleukin-10 (IL-10) is a potent anti-inflammatory and immunoregulatory cytokine, yet it remains unclear how IL-10 deficiency-induced immunosenescence participates in the development of PF. Methods: Firstly we evaluated the susceptibility to fibrosis and IL-10 expression in aged mice. Then 13-month-old wild-type (WT) and IL-10 knockout (KO) mice were subjected to bleomycin(BLM) and analyzed senescence-related markers by PCR, western blot and immunohistochemistry staining of p16, p21, p53, as well as DHE and SA-β-gal staining. We further compared 18-month-old WT mice with 13-month-old IL-10KO mice to assess aging-associated cell senescence and inflamation infiltration in both lung and BALF. Moreover, proliferation and apoptosis of alveolar type 2 cells(AT2) were evaluated by FCM, immunofluorescence, TUNEL staining, and TEM analysis. Recombinant IL-10 (rIL-10) was also administered intratracheally to evaluate its therapeutic potential and related mechanism. For the in vitro experiments, 10-week-old naïve pramily lung fibroblasts(PLFs) were treated with the culture medium of 13-month PLFs derived from WT, IL-10KO, or IL-10KO + rIL-10 respectively, and examined the secretion of senescence-associated secretory phenotype (SASP) factors and related pathways. Results: The aged mice displayed increased susceptibility to fibrosis and decreased IL-10 expression. The 13-month-old IL-10KO mice exhibited significant exacerbation of cell senescence compared to their contemporary WT mice, and even more severe epithelial-mesenchymal transition (EMT) than that of 18 month WT mice. These IL-10 deficient mice showed heightened inflammatory responses and accelerated PF progression. Intratracheal administration of rIL-10 reduced lung CD45 + cell infiltration by 15%, including a 6% reduction in granulocytes and a 10% reduction in macrophages, and increased the proportion of AT2 cells by approximately 8%. Additionally, rIL-10 significantly decreased α-SMA and collagen deposition, and reduced the expression of senescence proteins p16 and p21 by 50% in these mice. In vitro analysis revealed that conditioned media from IL-10 deficient mice promoted SASP secretion and upregulated senescence genes in naïve lung fibroblasts, which was mitigated by rIL-10 treatment. Mechanistically, rIL-10 inhibited TGF-β-Smad2/3 and PTEN/PI3K/AKT/ERK pathways, thereby suppressing senescence and fibrosis-related proteins. Conclusions: IL-10 deficiency in aged mice leads to accelerated cell senescence and exacerbated fibrosis, with IL-10KO-PLFs displaying increased SASP secretion. Recombinant IL-10 treatment effectively mitigates these effects, suggesting its potential as a therapeutic target for PF. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a major health problem worldwide and is usually detected in advanced stages, although it is highly treatable with early detection. The aim of this study was to examine the serum levels of various cytokines involved in the pathogenesis of CRC. The study included 29 patients and 30 healthy volunteers. Blood samples were collected twice from the patient group, before and after surgery, and these samples were evaluated for interleukin (IL) 4, 10, 23r, 37, 38, 40 and interferon (IFN) gamma levels. The results showed that IL-4 and IL-38 levels were significantly lower in the preoperative serum samples of the patient group compared to the control group (p < 0.001 and p = 0.01, respectively), while IL-4, IL-10, IL-38 and IL-40 levels increased significantly in the postoperative period (p = 0.004, p = 0.02, p = 0.03 and p = 0.004, respectively). These findings may contribute to the development of immunotherapy agents in the treatment of CRC. However, comprehensive studies on larger patient groups are needed to fully understand the role of cytokines in CRC pathogenesis. [ABSTRACT FROM AUTHOR]

Objective: To explore the molecular mechanism of dexmedetomidine (Dex) protecting ischemia/reperfusion (I/R) myocardium. Methods: Wild type mice were grouped into control (Control) group, sham operation (Sham) group, WT I/R group, WT Dex group, and Dectin-1 knock out mice were grouped into KO I/R group and KO Dex group in the in vivo study (n=6). TTC staining was used to determine the myocardial infarction area (%) of the above six groups of mice. HE staining and pathological analyze was used to determine the myocardial injury. Serum TNF-α, IL-6 and IL-10 levels in mice were detected by ELISA. Flow cytometry (FCM) was used to count and sort of infiltrating M2 macrophages and neutrophils in myocardium. qPCR assay was used to determine the Dectin-1 mRNA expression in the above sorted cells. Results: TTC results showed that there was no myocardial infarction in the mice of Control group and Sham group. Compared with the WT I/R group, the infarct volume was significantly lower in WT Dex group, KO I/R group and KO Dex group (P<0.05) . Compared with the KO I/R group, the infarct volume was reduced in KO Dex group (P< 0.05). The results of HE staining showed that the myocardial fibers of the WT I/R group of mice were disorderly arranged, with a large number of broken myocardial fibers, while the myocardial fibers of the WT Dex group, KO I/R group and KO Dex group of mice had a little breakage, the structural damage was not significant, and the myocardial arrangement was relatively neat. The degree of myocardi中国免疫学杂志 2024 年第 40 卷 al injury of mice in KO Dex group were less than that in KO I/R group mice. ELISA results showed that compared with Sham group, the serum TNF-α and IL-6 levels of the mice in WT I/R group were significantly increased, and the IL-10 level was significantly decreased. Compared with WT I/R group, serum TNF-α and IL-6 levels of the mice in WT Dex group and KO I/R group were significantly decreased, and IL-10 level was significantly increased. Compared with KO I/R group, the serum TNF-α and IL-6 levels of the mice in KO Dex group were significantly decreased, and the IL-10 level was significantly increased (P<0.05). FCM cell counting results showed that compared with Sham group, a large number of M2 macrophages and neutrophils were infiltrated in the myocardium of WT I/R group of mice (P<0.05) . Compared with WT I/R group, the M2 macrophages and neutrophils infiltrated in the myocardium were significantly decreased in WT Dex group, KO I/R group and KO Dex group of mice (P<0.05) . While there was no significant difference between the KO I/R group and the KO Dex group mice (P>0.05) . qPCR results showed that compared with Sham group, the expression level of Dectin-1 mRNA in the myocardial infiltrated M2 macrophages and neutrophils were significantly up-regulated in WT I/ R group of mice (P<0.05) . While compared with WT I/R group, the expression level of Dectin-1 mRNA in Dex group of mice was significantly lower (P<0.05) . Mice in KO I/R group and KO Dex group did not express Dectin-1. Conclusion: The protective mechanisms of Dex preconditioning on I/R injured myocardium involves reducing the infiltrating number of M2 macrophages and neutrophils in myocardium after I/R injury, which may be achieved by inhibiting the expression of Dectin-1. [ABSTRACT FROM AUTHOR]

M2-polarized, tumor-associated macrophages (TAMs) produce pro-tumorigenic and angiogenic mediators, such as interleukin-8 (IL-8) and IL-10. Leucine-rich repeat-containing protein 8 members (LRRC8s) form volume-regulated anion channels and play an important role in macrophage functions by regulating cytokine and chemokine production. We herein examined the role of LRRC8A in IL-8 and IL-10 expression in THP-1-differentiated M2-like macrophages (M2-MACs), which are a useful tool for investigating TAMs. In M2-MACs, the pharmacological inhibition of LRRC8A led to hyperpolarizing responses after a transient depolarization phase, followed by a slight elevation in the intracellular concentration of Ca2+. Both the small interfering RNA-mediated and pharmacological inhibition of LRRC8A repressed the transcriptional expression of IL-8 and IL-10, resulting in a significant reduction in their secretion. The inhibition of LRRC8A decreased the nuclear translocation of phosphorylated nuclear factor-erythroid 2-related factor 2 (Nrf2), while the activation of Nrf2 reversed the LRRC8A inhibition-induced transcriptional repression of IL-8 and IL-10 in M2-MACs. We identified the CCAAT/enhancer-binding protein isoform B, CEBPB, as a downstream target of Nrf2 signaling in M2-MACs. Moreover, among several upstream candidates, the inhibition of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) suppressed the Nrf2–CEBPB transcriptional axis in M2-MACs. Collectively, the present results indicate that the inhibition of LRRC8A repressed IL-8 and IL-10 transcription in M2-MACs through the NOX2–Nrf2–CEBPB axis and suggest that LRRC8A inhibitors suppress the IL-10-mediated evasion of tumor immune surveillance and IL-8-mediated metastasis and neovascularization in TAMs. [ABSTRACT FROM AUTHOR]

Cytokines coordinate the intricate choreography of the immune system, directing cellular activities that mediate inflammation, pathogen defense, pathology and tissue repair. Within this spectrum, the anti-inflammatory prowess of interleukin-10 (IL-10) predominates in immune homeostasis. In normal pregnancy, the dynamic shift of IL-10 across trimesters maintains maternal immune tolerance ensuring fetal development and pregnancy success. Unravelling the dysregulation of IL-10 in pregnancy complications is vital, particularly in the heightened inflammatory condition of preeclampsia. Of note, a reduction in IL-10 levels contributes to endothelial dysfunction. In human immunodeficiency virus (HIV) infection, a complex interplay of IL-10 occurs, displaying a paradoxical paradigm of being immune-protective yet aiding viral persistence. Genetic variations in the IL-10 gene further modulate susceptibility to HIV infection and preeclampsia, albeit with nuanced effects across populations. This review outlines the conceptual framework underlying the role of IL-10 in the duality of normal pregnancy and preeclampsia together with HIV infection, thus highlighting its regulatory mechanisms and genetic influences. Synthesizing these findings in immune modulation presents avenues for therapeutic interventions in pregnancy complications comorbid with HIV infection. [ABSTRACT FROM AUTHOR]

Trimetazidine (TMZ) is a promising emerging therapeutic piperazine derivative for renal pathologies. However, the nephroprotective mechanism of TMZ against heavy metal-induced toxicity is unknown. This study, therefore, aimed to explore whether TMZ could mitigate mercury-induced nephrotoxicity in rats. Rats were injected TMZ (3 mg/kg bw) and/or mercury chloride (HgCl2) (4 mg/kg bw) for 4 days (n = 6 rats per group). The blood analysis revealed marked increases in creatinine, urea and uric acid levels in HgCl2 group compared to the control. HgCl2 induced prominent decreases in renal superoxide dismutase (SOD), catalase (CAT), glutathione peroxide (GPx) activities compared to the control followed by marked increases in the levels of malondialdehyde (MDA), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), caspase-3 and caspase-9. Whereas the renal levels of anti-inflammatory cytokines interleukin-4 (IL-4) and interleukin-10 (IL-10) reduced considerably compared to the control. Contrarily, it was found that in the rats administered TMZ + HgCl2, levels of renal markers, MDA, TNF-α, IL-6 and caspases-3/-9 were prominently reduced compared to the HgCl2 group. The renal SOD, CAT, GPx, IL-4, and IL-10 were markedly elevated along with ameliorated histopathological lesions. On the whole, therefore, TMZ could be repurposed for blocking HgCl2 nephrotoxicity via inhibition of oxidative inflammation and apoptosis in rats. [ABSTRACT FROM AUTHOR]

Objective(s): The combination of TNF-α inhibitors and vitamin D in colitis remains to be elucidated. In the present study, we revealed the benefit of infliximab (IFX) and vitamin D in a mouse model of Ulcerative colitis (UC). Materials and Methods: A dextran sulfate sodium-induced colitis model was used. The therapeutic effect of the combination was evaluated by symptom and histopathology analysis. The synergistic mechanism was explored by detecting the regulatory effect of the combined therapy on Regulatory T cell (Treg) differentiation. Results: IFX and 1,25-dihydroxyvitamin D3 (VitD3) synergistically prevented the development of colitis by improving clinical signs, pathological and hematological manifestation, and inhibiting intestinal inflammation (decreasing TNF-α, IL-1β, and IL-6). Co-administration of IFX (2.5 mg/kg) with VitD3 or IFX (5.0 mg/kg) with VitD3 was more effective than administration of IFX (2.5 mg/kg, 5.0 mg/kg). There was no difference in therapeutic effect between IFX (5.0 mg/kg) and VitD3+ IFX (2.5 mg/kg) groups or between the VitD3+IFX (5.0 mg/kg) and VitD3+ Azathioprine (AZA) groups. VitD3 or combination therapy showed more powerful regulation of splenetic Treg differentiation and IL-10 production than IFX alone. Moreover, VitD3 alone or in combination induced higher levels of Foxp3 and IL-10 than IFX in colon tissue. In ulcerative colitis patients, serum VitD3 levels positively correlated with Treg levels. Conclusion: VitD3 and IFX synergistically inhibit colitis based on their powerful regulation of Treg differentiation. VitD3 combined with IFX is an alternative therapy for patients who are intolerant to standard doses of IFX or combination of IFX and AZA. [ABSTRACT FROM AUTHOR]

Purpose: To develop diagnostic recommendations for diffuse large B-cell vitreoretinal lymphoma (VRL) in Chinese patients. Methods: Retrospective observational case series. Seventy-three eyes of 40 VRL patients and 8 control patients were analyzed. Eighteen patients from Beijing Tongren Hospital and 46 patients from literature were involved as validations. Results: Diagnostic methods included (1) typical clinical manifestations; (2) vitreous cytology; (3) immunohistochemical examination of vitreous or choroid/retina; (4) aqueous humor or vitreous cytokine; (5) vitreous cell gene rearrangement; (6) vitreous flow cytometry. If patients meet (1)+(2)+(3), or if they meet (1), and two of (4), (5), (6) are positive, they can be diagnosed as VRL. The sensitivity and specificity values for accurate diagnosis were 0.975 and 1.00. One hundred percent eyes from Beijing Tongren Hospital and 92.7% eyes from literature can be diagnosed. Conclusion: We developed diagnostic recommendations for diffuse large B-cell VRL through vitreous cytology combined with multiple auxiliary examinations. [ABSTRACT FROM AUTHOR]

Background: Despite ongoing interventions, SARS-CoV-2 continues to cause significant global morbidity and mortality. Early diagnosis and intervention are crucial for effective clinical management. However, prognostic features based on transcriptional data have shown limited effectiveness, highlighting the need for more precise biomarkers to improve COVID-19 treatment outcomes. Methods: We retrospectively analyzed 149 clinical features from 189 COVID-19 patients, identifying prognostic features via univariate Cox regression. The cohort was split into training and validation sets, and 77 prognostic models were developed using seven machine learning algorithms. Among these, the least absolute shrinkage and selection operator (Lasso) method was employed to refine the selection of prognostic variables by ten-fold cross-validation strategy, which were then integrated with random survival forests (RSF) to build a robust COVID-19-related prognostic model (CRM). Model accuracy was evaluated across training, validation, and entire cohorts. The diagnostic relevance of interleukin-10 (IL-10) was confirmed in bulk transcriptional data and validated at the single-cell level, where we also examined changes in cellular communication between mononuclear cells with differing IL-10 expression and other immune cells. Results: Univariate Cox regression identified 43 prognostic features. Among the 77 machine learning models, the combination of Lasso and RSF produced the most robust CRM. This model consistently performed well across training, validation, and entire cohorts. IL-10 emerged as a key prognostic feature within the CRM, validated by single-cell transcriptional data. Transcriptome analysis confirmed the stable diagnostic value of IL-10, with mononuclear cells identified as the primary IL-10 source. Moreover, differential IL-10 expression in these cells was linked to altered cellular communication in the COVID-19 immune microenvironment. Conclusion: The CRM provides accurate prognostic predictions for COVID-19 patients. Additionally, the study underscores the importance of early IL-10 level testing upon hospital admission, which could inform therapeutic strategies. [ABSTRACT FROM AUTHOR]

Persistent malodor affects many people worldwide and is usually associated with poor dental hygiene. This pilot trial aimed to determine whether proper dental hygiene (DH) and a probiotic dietary supplement support oral health in volunteers with persistent malodor. Volunteers (n = 35) were randomly assigned to the probiotic or placebo cohort. The probiotic cohort (n = 20) brushed and flossed their teeth twice daily and used probiotics for 30 days; the placebo cohort (n = 15) followed the same hygiene practices and used the placebo. The intervention phase was followed by a 30-day follow-up period. Measured outcomes were malodor and tongue-coating scores, probiotic DNA levels, salivary cytokines, and salivary pH. DH and probiotics significantly decreased malodor (~50% during intervention) and tongue coating scores (~45% during intervention). These changes remained through the course of the trial. The probiotic DNA levels increased in the probiotic cohort and dropped in the placebo cohort after the intervention started. The malodor moderately correlated with the tongue coating P. acidilactici level. The addition of probiotics increased IL-10 levels during the intervention and decreased IL-8, TNF-α, and IL-6 by the end of the study. People with malodor may benefit from using DH and probiotics. Additional trials are needed to definitively establish the benefits of probiotic dietary supplements. [ABSTRACT FROM AUTHOR]

Elevated inflammatory activity is one possible pathway through which exposure to childhood adversity engenders risk for physical and psychiatric illnesses. Limited research has investigated the compounding effects of childhood and adolescent stress exposure on changes in circulating levels of inflammatory biomarkers. This study assessed whether childhood adversity interacted with chronic or acute stress during adolescence to affect the temporal trajectories of five inflammatory biomarkers across at least three blood draws in a diverse sample of adolescents (N = 134; observations = 462). Using multilevel modeling, the interaction of childhood adversity, time, and within-person variance of acute stressors significantly predicted trajectories of higher interleukin-10 levels, controlling for demographics, medication use, and body mass index. Adolescents with high levels of childhood adversity who were exposed to a higher frequency of acute stressors compared to their own average rate of stress exposure consistently had higher levels of IL-10 as they got older, but those with average and below frequency of acute stressors had decreasing trajectories of log IL-10 as they matured. The results demonstrate how events early in life shape biological responses to the adolescent environment. This study also highlights the importance of developmental timing on the bodys enhanced reactivity to acute and sustained stressors following childhood adversity.

Abstract Background Schizophrenia is a complex neuropsychiatric disorder. Growing evidence indicates that the activation of the inflammatory response system with interleukin (IL)-2, IL-4, IL-8, IL-10, and tumor necrosis factor-alpha (TNF-α) plays an important role in the pathogenesis of schizophrenia,. However, clinical data on cytokine levels in patients with schizophrenia treated with antipsychotics are inconsistent or inconclusive. In this study, we have examined inflammatory factors’ alterations and their relationship to changes in clinical symptoms before and after olanzapine treatment of drug-naive patients with first-episode schizophrenia. Methods We recruited 142 hospitalized patients with first-episode schizophrenia as a study group; blood samples were collected, and the patients were assessed for clinical symptoms at baseline and after 6 weeks of olanzapine treatment. One hundred individuals with no history of mental illness were also recruited as healthy controls. Blood samples were collected, and the serum levels of IL-2, IL-4, IL-8, IL-10, and TNF-α were determined using an enzyme cycling assay. The severity of clinical symptoms was assessed according to the Positive and Negative Syndrome Scale (PANSS). Results Individuals with schizophrenia had lower IL-8 levels and higher IL-10 levels than healthy controls (P

Objectives: This study explores the correlation between serum cholesterol, interleukin-10 (IL-10), macrophage migration inhibitory factor (MIF), and post-intracerebral hemorrhage (post-ICH) depression in patients with acute ICH. Methods: 35 patients with acute primary supratentorial ICH were recruited. Serum cholesterol, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDLC), and low-density lipoprotein cholesterol (LDLC), IL-10, and MIF were measured in the first morning after admission. Additionally, a 24-item Hamilton Depression Scale (HAMD-24) was used to detect depressive symptoms one week after admission. HAMD scores ≥ 8 indicated a diagnosis of post-ICH depression. Results: The levels of TC were significantly lower in ICH patients with depression compared to those without [169.26(139.23–215.67) mg/dL vs. 200.46(182.81–224.74) mg/dL, P = 0.010]. Similarly, levels of LDLC [102.18(78.39–137.28) mg/dL vs. 135.14(120.22–170.63) mg/dL, P = 0.001] and IL-10 [17.56(16.03–22.52) pg/mL vs. 31.17(23.42–37.53) pg/mL, P = 0.001] were also lower in patients with post-ICH depression. Furthermore, the levels of TC (r = -0.433, P = 0.009), TG (r = -0.345, P = 0.043), LDLC (r = -0.549, P = 0.001), and IL-10 levels (r = -0.603, P

Abstract Background Pulmonary fibrosis (PF) is an aging-related progressive lung disorder. The aged lung undergoes functional and structural changes termed immunosenescence and inflammaging, which facilitate the occurrence of fibrosis. Interleukin-10 (IL-10) is a potent anti-inflammatory and immunoregulatory cytokine, yet it remains unclear how IL-10 deficiency-induced immunosenescence participates in the development of PF. Methods Firstly we evaluated the susceptibility to fibrosis and IL-10 expression in aged mice. Then 13-month-old wild-type (WT) and IL-10 knockout (KO) mice were subjected to bleomycin(BLM) and analyzed senescence-related markers by PCR, western blot and immunohistochemistry staining of p16, p21, p53, as well as DHE and SA-β-gal staining. We further compared 18-month-old WT mice with 13-month-old IL-10KO mice to assess aging-associated cell senescence and inflamation infiltration in both lung and BALF. Moreover, proliferation and apoptosis of alveolar type 2 cells(AT2) were evaluated by FCM, immunofluorescence, TUNEL staining, and TEM analysis. Recombinant IL-10 (rIL-10) was also administered intratracheally to evaluate its therapeutic potential and related mechanism. For the in vitro experiments, 10-week-old naïve pramily lung fibroblasts(PLFs) were treated with the culture medium of 13-month PLFs derived from WT, IL-10KO, or IL-10KO + rIL-10 respectively, and examined the secretion of senescence-associated secretory phenotype (SASP) factors and related pathways. Results The aged mice displayed increased susceptibility to fibrosis and decreased IL-10 expression. The 13-month-old IL-10KO mice exhibited significant exacerbation of cell senescence compared to their contemporary WT mice, and even more severe epithelial-mesenchymal transition (EMT) than that of 18 month WT mice. These IL-10 deficient mice showed heightened inflammatory responses and accelerated PF progression. Intratracheal administration of rIL-10 reduced lung CD45 + cell infiltration by 15%, including a 6% reduction in granulocytes and a 10% reduction in macrophages, and increased the proportion of AT2 cells by approximately 8%. Additionally, rIL-10 significantly decreased α-SMA and collagen deposition, and reduced the expression of senescence proteins p16 and p21 by 50% in these mice. In vitro analysis revealed that conditioned media from IL-10 deficient mice promoted SASP secretion and upregulated senescence genes in naïve lung fibroblasts, which was mitigated by rIL-10 treatment. Mechanistically, rIL-10 inhibited TGF-β-Smad2/3 and PTEN/PI3K/AKT/ERK pathways, thereby suppressing senescence and fibrosis-related proteins. Conclusions IL-10 deficiency in aged mice leads to accelerated cell senescence and exacerbated fibrosis, with IL-10KO-PLFs displaying increased SASP secretion. Recombinant IL-10 treatment effectively mitigates these effects, suggesting its potential as a therapeutic target for PF. Graphical Abstract

BackgroundGuidelines for limited-stage human immunodeficiency virus-associated Kaposi sarcoma (AIDS/KS) recommend antiretroviral therapy (ART) as initial treatment. However, many such individuals show worsening KS and require additional chemotherapy. Methods to identify such patients are lacking.SettingWe studied whether serum levels of biomarkers associated with angiogenesis, systemic inflammation, and immune activation, which are elevated in HIV-infected individuals and implicated in the development of KS, could prospectively identify individuals with limited-stage AIDS-KS who would benefit from chemotherapy administered with ART.MethodsSerum specimens were obtained from participants in a randomized trial evaluating the value of adding oral etoposide chemotherapy to ART in treatment-naïve people with limited-stage AIDS-KS in resource-limited settings. Serum biomarkers of inflammation (C-reactive protein [CRP], interleukin [IL]-6, IL-8, IL-10, granulocyte colony stimulating factor, soluble tumor necrosis factor receptor-2), immune system activation (soluble IL-2 receptor alfa, C-X-C motif chemokine ligand 10/interferon gamma-induced protein 10, C-C motif ligand 2/monocyte chemoattractant protein 1), and angiogenesis (vascular endothelial growth factor, matrix metalloproteinase-2, -9, endoglin, hepatocyte growth factor) were measured at entry to determine whether baseline levels are associated with KS response. On-treatment changes in biomarker levels were determined to assess how etoposide modifies the effects of ART.ResultsPretreatment CRP and IL-10 were higher in those whose KS progressed, and lowest in those who had good clinical responses. Pretreatment CRP, IL-6, and soluble tumor necrosis factor receptor-2 showed significant associations with KS progression at the week-48 primary endpoint. Immediate etoposide led to lower inflammation biomarker levels compared with ART alone. Early KS progression was associated with elevated pretreatment levels of inflammation-associated biomarkers and increasing levels post-treatment.ConclusionsQuantifying serum biomarkers, especially CRP, may help identify persons with AIDS-KS who would benefit from early introduction of chemotherapy in addition to ART.

BACKGROUND: Diabetic ulcers are a common complication of diabetes mellitus, which is manifested as foot ulcers complicated with infection, long treatment cycle, high disability rate and mortality rate, and brings a heavy burden to patients and social care. OBJECTIVE: To review the mechanism of action and the latest treatment progress of traditional Chinese medicine (TCM) in the treatment of diabetic ulcers, and to provide a basis for further theoretical research and clinical application. METHODS: CNKI, WanFang Database and PubMed database were searched for relevant literature using the keywords of “diabetic ulcer, medicinal herb, inflammation, interleukin-1β, interleukin-6, tumor necrosis factor, hypersensitive C-reactive protein, γ-interferon, interleukin-4, interleukin-10” in Chinese and English, respectively. The relevant literature in recent years was searched, and finally 75 articles were included for review. RESULTS AND CONCLUSION: The high glucose environment of the body will increase the level of pro-inflammatory cytokines, so that diabetic ulcer wounds are in a state of chronic inflammatory response for a long time, and difficult to heal or even not heal. TCM has summed up a lot of experience in the long-term struggle with diabetic ulcer. At present, TCM divides diabetic ulcers into four syndrome types: dampness and heat poison syndrome, blood and blood stasis obstruction pattern, heat poison injury Yin pattern, and Qi and blood deficiency syndrome, as well as representative prescriptions for treatment. According to their clinical characteristics, diabetic ulcers can be also divided into three stages: primary, middle and late stages. Different treatment methods are proposed: “clear method,” “warm and clear combined use” and “maintenance method.” Under the guidance of dialectical typing and staging of TCM, TCM monomers, extracts and compounds inhibit the inflammatory response and promote the healing of diabetic ulcers by down-regulating the expression of pro-inflammatory factors and/or up-regulating the expression of anti-inflammatory factors. Compared with modern medicine, TCM has significant advantages in the treatment of diabetic ulcers. There are many TCM monomers, extracts and compounds for the treatment of diabetic ulcers, such as angelica, curcumin, improved Chonghe ointment, Sanhuang blood exhaustion prescription and sore-ulcer I. formula, etc. It has been found that TCM for the treatment of diabetic ulcers is mainly heatclearing and detoxifying, invigorating blood circulation and removing blood stasis, and amassing sores and muscle-building drugs, and the frequency of use, treatment scope and therapeutic effect of TCM compounds are obviously better than those of TCM monomers and extracts. Among them, the most commonly used are the Sanhuang blood exhaustion prescription and the sore-ulcer I as well as prescription for the treatment of damp heat toxicity syndrome and Zizhu ointment for the treatment of non-ischemic diabetic ulcers. However, there are also some shortcomings in the treatment of diabetic ulcers with TCM. First, there are few clinical syndrome studies on diabetic ulcers. Secondly, there are a wide variety of TCM monomers, extracts and compounds for the treatment of diabetic ulcers, and the relevant research is insufficiently in-depth. Finally, the research on the mechanism underlying TCM treatment of diabetic ulcers is still in the preliminary exploration stage, and the mechanism of action still needs to be further explored. In the future, it is necessary to strengthen the research on the pharmacology of TCM and the clinical syndrome of diabetic ulcers, analyze the potential targets and related signaling pathways of TCM in the treatment of diabetic ulcers, give full play to the therapeutic advantages of TCM with multiple targets, multiple pathways, multiple levels and multiple systems, and develop TCM with significant efficacy, active ingredients and clear targets. [ABSTRACT FROM AUTHOR]

Using probiotics represents a potential solution to post-weaning diarrheal diseases in piglets on commercial farms. The gastrointestinal tract of wild boars serves as a promising reservoir of novel lactic acid bacteria with suitable probiotic characteristics. In this study, we isolated eight bacterial strains from the intestinal content of wild boars identified as representatives of the species Bifidobacterium apri, Lactobacillus amylovorus, and Ligilactobacillus salivarius. These isolates underwent in vitro analysis and characterisation to assess their biological safety and probiotic properties. Analysis of their full genome sequences revealed the absence of horizontally transferrable genes for antibiotic resistance. However, seven out of eight isolates harboured genes encoding various types of bacteriocins in their genomes, and bacteriocin production was further confirmed by mass spectrometry analysis. Most of the tested strains demonstrated the ability to inhibit the growth of selected pathogenic bacteria, produce exopolysaccharides, and stimulate the expression of interleukin-10 in porcine macrophages. These characteristics deem the isolates characterised in this study as potential candidates for use as probiotics for piglets during the post-weaning period.

Abstract Atopic dermatitis (AD) presents significant therapeutic challenges due to its poorly understood etiology. Eosinophilia, a hallmark of allergic inflammation, is implicated in AD pathogenesis. Interleukin-10 (IL-10)-producing regulatory B (Breg) cells exhibit potent anti-inflammatory effects. However, their role in controlling AD-related eosinophilia is not well understood. To investigate the impact of eosinophils on AD, we employed IL-5Rα-deficient (Il5ra −/− ) mice, which lack functional eosinophils. Induction of AD in these mice resulted in attenuated disease symptoms, underscoring the critical role of eosinophils in AD development. Additionally, the adoptive transfer of purified Breg cells into mice with AD significantly alleviated disease severity. Mechanistic studies revealed that IL-10 produced by Breg cells directly inhibits eosinophil activation and infiltration into the skin. In vitro experiments further confirmed that Breg cells inhibited eosinophil peroxidase secretion in an IL-10-dependent manner. Our collective findings demonstrate that IL-10 from Breg cells alleviates AD by suppressing eosinophil activation and tissue infiltration. This study elucidates a novel regulatory mechanism of Breg cells, providing a foundation for future Breg-mediated therapeutic strategies for AD.

Abstract Background Generalized anxiety disorder (GAD) is a devastating mental health condition characterized by constant, uncontrolled worrying. Recent hypotheses indicate that pro-inflammatory cytokines and chemokines are potential contributors to the pathogenesis of GAD. Here, we aimed to assess the role of interleukin-2 (IL-2) and interleukin-10 (IL-10) in the pathophysiology and development of GAD. Methods This study recruited 50 GAD patients diagnosed according to the DSM-5 criteria and 38 age-sex-matched healthy controls (HCs). A qualified psychiatrist evaluated all study subjects. The socio-demographic and clinical characteristics of the study population were determined using pre-structured questionnaires or interviews, and cytokine serum levels were estimated using commercially available ELISA kits. Results We observed reduced serum IL-10 levels in GAD patients compared to HCs (33.69 ± 1.37 pg/ml vs. 44.12 ± 3.16 pg/ml). Also, we observed a significant negative correlation between altered IL-10 levels and GAD-7 scores (r=-0.315, p = 0.039). Moreover, IL-10 serum measurement exhibited good predictive value in receiver operating characteristics (ROC) analysis with an area under the curve (AUC) value of 0.793 (p 0.05) exhibited by IL-2 serum measurement in ROC analysis further supported that IL-2 might not be associated with GAD. Conclusion This study provides new insights into the complex interplay between anti-inflammatory cytokines and GAD pathogenesis. Based on the present findings, we can assume that IL-10 but not IL-2 may be associated with the pathophysiology and development of GAD. However, further research with a larger population size and longitudinal design is required to confirm the potential diagnostic efficacy of IL-10.

Conventional CD4pos regulatory T (Treg) cells characterized by expression of the key transcription factor forkhead box P3 (FoxP3) are crucial to control immune responses, thereby maintaining homeostasis and self-tolerance. Within the substantial population of non-conventional T cell receptor (TCR)αβpos CD4negCD8αneg double-negative (dn) T cells of dogs, a novel FoxP3pos Treglike subset was described that, similar to conventional CD4pos Treg cells, is characterized by high expression of CD25. Noteworthy, human and murine TCRαβpos regulatory dn T cells lack FoxP3. Immunosuppressive capacity of canine dn T cells was hypothesized based on expression of inhibitory molecules (interleukin (IL)-10, cytotoxic T-lymphocyte associated protein 4, CTLA4). Here, to verify their regulatory function, the dnCD25pos (enriched for FoxP3pos Treg-like cells) and the dnCD25neg fraction, were isolated by fluorescence-activated cell sorting from peripheral blood mononuclear cells (PBMC) of Beagle dogs and analyzed in an in vitro suppression assay in comparison to conventional CD4posCD25pos Treg cells (positive control) and CD4posCD25neg T cells (negative control). Canine dnCD25pos T cells suppressed the Concanavalin A-driven proliferation of responder PBMC to a similar extent as conventional CD4posCD25pos Treg cells. Albeit to a lesser extent than FoxP3-enriched dn and CD4posCD25pos populations, even dnCD25neg T cells reduced the proliferation of responder cells. This is remarkable, as dnCD25neg T cells have a FoxP3neg phenotype comparable to non-suppressive CD4posCD25neg T cells. Both, CD25pos and CD25neg dn T cells, can mediate suppression independent of cell-cell contact and do not require additional signals from CD4posCD25neg T cells to secrete inhibitory factors in contrast to CD4posCD25pos T cells. Neutralization of IL-10 completely abrogated the suppression by dnCD25pos and CD4posCD25pos Treg cells in a Transwell™ system, while it only partially reduced suppression by dnCD25neg T cells. Taken together, unique canine nonconventional dnCD25pos FoxP3pos Treg-like cells are potent suppressor cells in vitro. Moreover, inhibition of proliferation of responder T cells by the dnCD25neg fraction indicates suppressive function of a subset of dn T cells even in the absence of FoxP3. The identification of unique immunoregulatory nonconventional dn T cell subpopulations of the dog in vitro is of high relevance, given the immunotherapeutic potential of manipulating regulatory T cell responses in vivo. [ABSTRACT FROM AUTHOR]

Proinflammatory cytokines are implicated in promoting neurodegeneration in multiple sclerosis (MS) by affecting excitatory and inhibitory transmission at central synapses. Conversely, the synaptic effects of anti-inflammatory molecules remain underexplored, despite their potential neuroprotective properties and their presence in the cerebrospinal fluid (CSF) of patients. In a study involving 184 newly diagnosed relapsing-remitting (RR)-MS patients, we investigated whether CSF levels of the anti-inflammatory interleukin (IL)-10 were linked to disease severity and neurodegeneration measures. Additionally, we examined IL-10 impact on synaptic transmission in striatal medium spiny neurons and its role in counteracting inflammatory synaptopathy induced by IL-1β in female C57BL/6 mice with experimental autoimmune encephalomyelitis (EAE). Our findings revealed a significant positive correlation between IL-10 CSF levels and changes in EDSS (Expanded Disability Status Scale) scores one year after MS diagnosis. Moreover, IL-10 levels in the CSF were positively correlated with volumes of specific subcortical brain structures, such as the nucleus caudate. In both MS patients' CSF and EAE mice striatum, IL-10 and IL-1β expressions were upregulated, suggesting possible antagonistic effects of these cytokines. Notably, IL-10 exhibited the ability to decrease glutamate transmission, increase GABA transmission in the striatum, and reverse IL-1β-induced abnormal synaptic transmission in EAE. In conclusion, our data suggest that IL-10 exerts direct neuroprotective effects in MS patients by modulating both excitatory and inhibitory transmission and attenuating IL-1β-induced inflammatory synaptopathy. These findings underscore the potential therapeutic significance of IL-10 in mitigating neurodegeneration in MS. [ABSTRACT FROM AUTHOR]

The experiment aimed to study the effects of different levels of compound probiotics on the growth performance, immunity, and intestinal barrier function of piglets. A total of 160 'Duroc×Landrace×Yorkshire' weaned piglets at 21 days of age were randomly divided into four groups, with four replicates in each group, and 10 piglet in each replicate. The control group, test group 1, test group 2, and test group 3 were fed diets containing 0, 0.1%, 0.2%, and 0.4% compound probiotics, respectively. The preliminary trial lasted for one week, and the formal experiment lasted for six weeks. The results showed that compared with the control group, the final weight and average daily weight gain of piglets in the test group 2 and group 3 increased significantly by 13.64%, 11.81% and 20.43%, 16.22% (P<0.05), respectively, and the average daily feed intake increased by 6.98%, 7.71% (P<0.05). The feed to gain ratio of all the test groups decreased by 7.54%, 11.06%, and 7.54% (P<0.05), and the diarrhea rate decreased by 29.04%, 44.03%, and 49.53% (P<0.05). Compared with the control group, the levels of IgA and IgG in the serum of piglets in the test group 2 and group 3 increased significantly (P<0.05). The level of IL-6 decreased significantly (P<0.05), the level of IL-10 in the serum of all the test groups increased significantly (P<0.05), and the level of TNF-α in the serum of piglets in the test group 2 decreased significantly (P<0.05). Compared with the control group, the level of D-LA in the test group 2 decreased significantly (P<0.05), and the levels of ET in the test group 2 and group 3 decreased significantly (P<0.05). The expression of Occludin in the ileum of the test group 2 and group 3 increased significantly (P<0.05), the expression of ZO-1 and TRAF6 in the test group 2 increased significantly (P<0.05), the expression of Occludin, TLR2, and NF-κB in the colon of the test group 2 and group 3 increased significantly (P<0.05), and the expression of TLR4 in the test group 2 increased significantly (P<0.05). The study indicates that the addition of an appropriate amount of compound probiotics to the diet can improve the growth performance and immunity of piglets and enhance the function of the intestinal mucosal barrier. The suitable addition level of compound probiotics is 0.2%. [ABSTRACT FROM AUTHOR]

Background: Inflammation plays a critical role in myocardial infarction as a critical process in the development of heart failure, involving the development of cardiac fibrosis. Colchicine is a well-established anti-inflammatory drug, but its scientific application in controlling post-acute myocardial infarction (AMI) inflammatory processes has not been established. IL-10 is a key cytokine in modulating inflammatory responses, underscoring its potential as a crucial therapeutic target of colchicine. The objective was to explore the protective role of IL-10 modulated by colchicine in myocardial healing and repair following AMI, particularly cardiac fibrosis. Methods: The predicted protein of colchicine was assessed using WAY2DRUG PASS as probability active value. Proteins associated with colchicine, cardiac fibrosis, and acute myocardial infarction were analyzed with DisGeNET and Open Target databases. Analysis and visualization of protein–protein interactions were conducted using STRING and Cytoscape. A 3T3 cell line treated with CoCl2 was used to mimic hypoxic. HIF-1α and IL-10 expression were measured by flow cytometry and analyzed using a one-way ANOVA test. This observational clinical trial examined acute myocardial infarction patients undergoing immediate and delayed primary percutaneous coronary interventions. Subjects were randomized into control groups receiving placebo and intervention groups treated with colchicine. Assessments occurred at 24 h and five days after the intervention. IL-10 expression in the clinical trial was measured by ELISA and analyzed using a T-test. Results: Colchicine demonstrates promising bioactivity in treating acute myocardial infarction, with notably activity values highlighting its probable role as a tubulin antagonist (0.744), beta-tubulin antagonist (0.673), and NOS2 inhibitor (0.529). Its primary action targets IL-10, with the protein–protein interactions analysis indicating interactions between IL-10 and key inflammatory mediators—IL-1β, IFN-γ, CCL2, TNF, and TGF-β1—during acute myocardial infarction and cardiac fibrosis. Hypoxic conditions in the CoCl2-induced 3T3 cell model show significantly elevated HIF-1α compared to controls (p < 0.0001). Colchicine use significantly increased IL-10 expression in CoCl2-treated cells (p < 0.0001) and in AMI patients within five days (p < 0.05). Conclusions: Colchicine may bolster the anti-inflammatory response post-myocardial infarction by activating IL-10 pathways in fibroblasts and in clinical settings, potentially reducing inflammation after AMI. Further investigation into broader aspects of this pathway, particularly in cardiac fibroblasts, is required. [ABSTRACT FROM AUTHOR]

Simple Summary: There are no reliable prognostic biomarkers for ovarian cancer. The immune tumor suppressive marker interleukin-10 has been shown to be elevated in cancer, specifically in ovarian cancer. This study aims to correlate interleukin-10 levels in the ascites and sera of ovarian cancer patients to correlate with cancer-related data and outcomes. Our findings suggest a prognostic role for interleukin-10 that may be related to its immunosuppressive function in the tumor microenvironment. Future studies are needed to validate these results. This study highlights a potential target for novel therapeutic approaches. Interleukin-10 (IL-10) has been shown to be present at high levels in the ascites of ovarian cancer (OC) patients; however, little is known about its prognostic value. We sought to correlate IL-10 levels in ascites and sera of OC patients with clinicopathologic characteristics and oncologic outcomes. IL-10 levels and clinical data from biobanked ascites and serum samples of OC patients were evaluated. Receiver operating characteristic curves were used to quantify marker performance and identify IL-10-high and IL-10-low groups. Correlations between IL-10 levels and clinicopathologic data were performed. Survival outcomes were calculated, while the factors affecting them were also investigated. A total of 106 patients had ascites samples, of which 44 serum samples were also available. Mean ascites IL-10 levels were significantly higher in patients with serous histology compared to endometrioid histology (p = 0.024). Fold-change in ascites IL-10 during treatment positively correlated with clinical response, as determined by a change in serum cancer antigen (CA)-125 levels (p = 0.0126). Median progression-free survival (PFS) and overall survival (OS) were shorter in patients with high compared with low ascites IL-10 levels (PFS: 18 versus 60 months; p = 0.007, OS: 42 versus 85 months; p = 0.029). A significant positive correlation was seen between ascites and sera IL-10 levels (p = 0.019). In multivariable analyses, a high ascites IL-10 level was associated with a significantly worse prognosis (PFS hazard ratio (HR) = 1.93; p = 0.02). Patients with high ascites levels of IL-10 have worse outcomes, which are likely reflective of the immunosuppressive effect of IL-10. This highlights its potential role as an immunomodulator in the tumor microenvironment, leading to OC immune evasion. [ABSTRACT FROM AUTHOR]

Endometriosis is known to be a chronic, debilitating disease. The pathophysiological mechanisms of endometriosis development include local chronic inflammation and a certain degree of local immune deficit. We investigated the relationship between the endometriosis severity, IL-8, IL-10, BDNF, VEGF-A serum and tissue levels, patient-related pain, and physical activity in a cohort of 46 patients diagnosed with endometriosis who underwent surgery. The same panel of biomarkers was investigated in a control group of 44 reproductive-aged patients with non-endometriotic gynecological pathology who underwent surgical intervention. Our data show a high statistical significance between tissue expression of IL-8, IL-10, patient-related pain, and the severity of endometriosis. No relationship was identified between serum or tissue levels of VEGF-A and BDNF and the severity of endometriosis. These results validate the presence of local chronic inflammation and immune deficit, thereby creating, alongside other studies in the field, an opportunity for the development of innovative and personalized treatment approaches in endometriosis. [ABSTRACT FROM AUTHOR]

Diabetic wounds present a significant challenge in regenerative medicine due to impaired healing, characterized by prolonged inflammation and deficient tissue repair, primarily caused by a skewed pro‐inflammatory macrophage phenotype. This study investigates the therapeutic potential of interleukin‐10 (IL‐10) chemically modified mRNA (modRNA)‐enriched human adipose‐derived multipotent stromal cells (hADSCs) in a well‐established murine model of diabetic wounds. The modRNAs used in this study were chemically modified using N1‐methylpseudouridine‐5′‐triphosphate (m1Ψ) by substituting uridine‐5‐triphosphate. In vitro experiments demonstrated that IL‐10 modRNA‐transfected hADSCs effectively modulated macrophage polarization towards an anti‐inflammatory phenotype. In vivo experiments with a well‐established murine model demonstrated that transplantation of hADSCsmodIL‐10 on postoperative day 5 (POD5) significantly improved wound healing outcomes, including accelerated wound closure, enhanced re‐epithelialization, promoted M2 polarization, improved collagen deposition, and increased neovascularization. This study concludes that IL‐10 modRNA‐enriched hADSCs offer a promising therapeutic approach for diabetic wound healing, with the timing of IL‐10 administration playing a crucial role in its effectiveness. These cells modulate macrophage polarization and promote tissue repair, demonstrating their potential for improving the management of diabetic wounds. [ABSTRACT FROM AUTHOR]

Background: The study aimed to investigate the association of IL-6 and IL-10 polymorphisms with susceptibility to glaucoma by analyzing all relevant individual studies. Materials and Methods: Relevant articles were gathered from PubMed, Web of Science, Embase, WanFang, and CNKI databases up to 15 October 2023. Odds ratios (ORs) were used to evaluate the association strengths, along with 95% confidence intervals (CIs). Results: Seven case-control studies involving 1408 cases and 1789 controls on the IL-6 -174 G>C polymorphism, and three studies with 675 cases and 1100 controls on the IL-6 -572 G>C were included. Moreover, three separate studies, each comprising 442 cases and 672 controls, investigated the IL-10 -592C>A, −819T>C, and −1082A>G polymorphisms. The combined data indicated a significant association between −592C>A, −819T>C, and −1082A>G at IL-10 gene and IL-6 -572 G>C with glaucoma susceptibility, with no correlation found for IL-6 -174 G>C. Conclusions: The study found that IL-10 -592C>A, −819T>C, −1082A>G, and IL-6 -572 G>C polymorphisms were linked to glaucoma risk. However, no significant association was observed for IL-6 -174 G>C. These findings imply a possible connection between genetic variations in these genes and glaucoma risk. Further research is crucial to fully understand the underlying mechanisms and their significance in managing and preventing glaucoma. [ABSTRACT FROM AUTHOR]

Background: Hepatotoxicity is an adverse complication in 5-Fluorouracil cancer treatment. Inflammation, oxidative stress, apoptosis and DNA damage are essential in the pathogenesis of liver damage. The present study evaluated the ameliorative effect of Naringenin (NG) in 5-FU at two different intervals in hepatic damage. Methods: Total (n=48) Albino Wistar rats were divided into 4 groups (N=12), Control-normal saline (group-1) per oral, 5-FU (group-2) @ 20 mg/kg b.wt was injected intraperitoneal (IP) for first 5 days, NG (group-3) @100 mg/kg b. wt/day orally for 28 days. Another group-4 was concurrently treated with NG along with 5-FU for 28 days and sacrificed on the 14th and 28th day of the experiment. Result: On exposure to 5-FU, biochemical variation of liver enzymes (ALT, AST, ALP and TP) were significantly increased while NG treatment significantly reduced these biomarkers in group 2 on 14th day and 28th day of the experiment. Furthermore, NG treatment significantly reduced lipid peroxidation and increases the antioxidant profile. It also significantly reduced elevated concentrations of pro-inflammatory cytokines like tumour necrosis factor (TNF-a), interleukin -1ß (IL-1ß), interleukin-6 (IL-6) with increased concentrations of interleukin-10 (IL-10) along with reduced immunohistochemical expression of nuclear factor kappa light chain enhancer of activated B cells (NF-κB) and Caspases-3 (Cas-3) by NG. On histopathology, pathological lesions were observed to support biochemical variations in group-2 rats. In group-4 rats, NG ameliorates liver enzymes, inflammatory cytokines and oxidative indices through an anti-oxidant, anti-inflammatory and anti-apoptotic property. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular diseases (CVDs) represent major medical and socio-economic challenges worldwide. There is substantial evidence that CVD is closely linked to inflammatory changes triggered by a complex cytokine network. In this context, interleukin 10 (IL-10) plays an important role as a pleiotropic cytokine with an anti-inflammatory capacity. In this study (a substudy of ClinTrials.gov, identifier: NCT01045070), the prognostic relevance of IL-10 levels and IL-10 haplotypes (rs1800896/rs1800871/rs1800872) was assessed regarding adverse cardiovascular outcomes (combined endpoint: myocardial infarction, stroke/transient ischemic attack, cardiac death and death according to stroke) within a 10-year follow-up. Patients and methods: At baseline, 1002 in-patients with CVD were enrolled. Serum levels of IL-10 were evaluated utilizing flow cytometry (BD™ Cytometric Bead Array). Haplotype analyses were carried out by polymerase chain reactions with sequence-specific primers (PCR-SSP). Results: In a survival analysis, IL-10 haplotypes were not proven to be cardiovascular prognostic factors in a 10-year follow-up (Breslow test: p = 0.423). However, a higher IL-10 level was associated with adverse cardiovascular outcomes (Breslow test: p = 0.047). A survival analysis considering adjusted hazard ratios (HRs) could not confirm this correlation (Cox regression: adjusted HR = 1.26, p = 0.168). Conclusion: In the present study, an elevated IL-10 level but not IL-10 haplotypes was linked to adverse cardiovascular outcomes (10-year follow-up) in a cohort of CVD patients. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is a multifactorial disease influenced by genetic, environmental, and immunological factors. Genetic polymorphisms in the interleukin-10 (IL-10) gene have been implicated in PCa susceptibility, development, and progression. This study aims to assess the contributions of three IL-10 promoter single nucleotide polymorphisms (SNPs), A-1082G (rs1800896), T-819C (rs3021097), and A-592C (rs1800872), to the risk of PCa in Taiwan. The three IL-10 genotypes were determined using PCR-RFLP methodology and were evaluated for their contributions to PCa risk among 218 PCa patients and 436 non-PCa controls. None of the three IL-10 SNPs were significantly associated with the risks of PCa (p all > 0.05) in the overall analyses. However, the GG at rs1800896 combined with smoking behavior was found to significantly increase the risk of PCa by 3.90-fold (95% confidence interval [95% CI] = 1.28–11.89, p = 0.0231). In addition, the rs1800896 AG and GGs were found to be correlated with the late stages of PCa (odds ratio [OR] = 1.90 and 6.42, 95% CI = 1.05–3.45 and 2.30–17.89, p = 0.0452 and 0.0003, respectively). The IL-10 promoter SNP, A-1082G (rs1800896), might be a risk factor for PCa development among smokers and those at late stages of the disease. These findings should be validated in larger and more diverse populations. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: We assessed the levels of Interleukin-10 (IL-10), Interleukin-12 (IL-12), and Interleukin-18 (IL-18) in the gingival crevicular fluid (GCF) of subjects with advanced periodontitis (SIII-SIV) compared to healthy controls and evaluated their correlations with clinical measurements. Methods: This cross-sectional study involved subjects (n = 60) diagnosed with stage III grade B-C (n = 13) to stage IV grade C (n = 17) periodontitis, and periodontally healthy controls (n = 30). Clinical periodontal measurements involved full-mouth. The concentrations of IL-10, IL-12, and IL-18 were determined using enzyme-linked immunosorbent assay (ELISA). Results: There were no significant differences in IL-12 level and IL-18/IL-10 ratio between the healthy and periodontitis groups (p = 0.413, p = 0.636, respectively). The IL-10 and IL-18 levels were significantly higher in the periodontitis group than in controls (p < 0.001, p < 0.001, respectively). Significant associations were observed between the periodontitis and IL-10 and IL-18 levels (OR = 1.46, %95 CI 1.19–1.795; OR = 1.13, %95 CI 1.059–1.207, respectively) (p < 0.001, p < 0.001, respectively). Conclusions: There was a correlation between pocket depth and the presence of IL-18 and a strong association between periodontitis and a high level of IL-18. However, there were no direct correlations among the three biomarkers and IL-18/IL-10 ratio, indicating that their roles in periodontal health are complex and multidimensional. Clinical relevance: Understanding the cytokine dynamics in GCF provides valuable insights into their potential clinical implications for periodontal disease diagnosis, risk assessment, and tailored therapeutic interventions. [ABSTRACT FROM AUTHOR]

Using probiotics represents a potential solution to post-weaning diarrheal diseases in piglets on commercial farms. The gastrointestinal tract of wild boars serves as a promising reservoir of novel lactic acid bacteria with suitable probiotic characteristics. In this study, we isolated eight bacterial strains from the intestinal content of wild boars identified as representatives of the species Bifidobacterium apri, Lactobacillus amylovorus, and Ligilactobacillus salivarius. These isolates underwent in vitro analysis and characterisation to assess their biological safety and probiotic properties. Analysis of their full genome sequences revealed the absence of horizontally transferrable genes for antibiotic resistance. However, seven out of eight isolates harboured genes encoding various types of bacteriocins in their genomes, and bacteriocin production was further confirmed by mass spectrometry analysis. Most of the tested strains demonstrated the ability to inhibit the growth of selected pathogenic bacteria, produce exopolysaccharides, and stimulate the expression of interleukin-10 in porcine macrophages. These characteristics deem the isolates characterised in this study as potential candidates for use as probiotics for piglets during the post-weaning period. [ABSTRACT FROM AUTHOR]

We discovered high-titer neutralizing autoantibodies against interleukin-10 in a child with infantile-onset inflammatory bowel disease (IBD), a phenocopy of inborn errors of interleukin-10 signaling. After B-cell-depletion therapy and an associated decrease in the anti-interleukin-10 titer, conventional IBD therapy could be withdrawn. A second child with neutralizing anti-interleukin-10 autoantibodies had a milder course of IBD and has been treated without B-cell depletion. We conclude that neutralizing anti-interleukin-10 autoantibodies may be a causative or modifying factor in IBD, with potential implications for therapy. [ABSTRACT FROM AUTHOR]