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Viral infections can be acute or chronic, with the immune system pivotal in immunopathogenesis. The potential reversibility of inflammation post-viral elimination is of current interest. This study compares the dynamics of soluble inflammatory mediators (SIM) during and after respiratory infections with SARS-CoV-2 and blood-borne acute and chronic hepatitis C virus (HCV) infections. The study included patients with acute HCV (n = 29), chronic HCV (n = 54), and SARS-CoV-2 (n = 39 longitudinal, n = 103 cross-sectional), along with 30 healthy controls. Blood samples were collected at baseline, end of treatment/infection, and during follow-up (up to 9 months). SIMs were quantified using the HD-SP-X Imaging and Analysis System™. At baseline, SIM profiles in acute SARS-CoV-2 and HCV infections were significantly elevated compared with controls. During follow-up, SIM decline was less pronounced in acute and chronic HCV infections after successful therapy than in SARS-CoV-2 infections. Most SIM in the SARS-CoV-2 cohort normalized within 3 months. In chronic HCV, SIM were higher in cirrhotic than noncirrhotic patients post-HCV elimination. Dynamics of SIM after viral elimination vary between blood-borne acute and chronic HCV infections and respiratory SARS-CoV-2 infections. Immunological imprints 3–9 months after HCV elimination appear more pronounced than after SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Introduction: Several studies investigated the implication of the gut microbiota (GM) in the formation and progression of aneurysms, suggesting a key role for GM metabolites in aneurysmal pathogenesis and prognosis. Aim: This systematic review aims to collect key findings concerning the impact of gut bacterial compositions, GM-related metabolites, probiotics administration, and inflammatory markers in aneurysmal development and rupture. Methods: A PubMed, Medline, Embase, and Web of Science database search was conducted in accordance with PRISMA guidelines for systematic reviews, targeting all studies assessing the GM's role in aneurysms till 2023. Results: Data from 19 out of 292 non-duplicated studies were included. Based on the published literature, aneurysmal incidents in several locations were accompanied by an alteration in specific intestinal bacteria that may affect the prognosis of the aneurysm. The gut dysbiosis was also accompanied by modifications in the metabolic pathways. Hence, the administration of specific probiotics showed a significant implication in reversing the GM-related changes that were affecting the aneurysm, leading to a decrease in its severity, a better prognosis, and even serving as a prophylactic approach. Conclusions: The outcomes of this review highlight the role of GM in the pathogenesis of aneurysms, assessing some involved mechanistic pathways such as gut dysbiosis, inflammation, and the alteration of gut-derived metabolites levels, which orient new research on developing therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background/Objectives: Cow's milk allergy is one of the most common food allergies in children, and its pathomechanism is still under investigation. Recently, an increasing number of studies have linked food allergy to intestinal barrier dysfunction. The present study aimed to investigate changes in the intestinal microenvironment during the development of β-lactoglobulin (β-lg) allergy under conditions of early intestinal dysfunction. Methods: BALB/c mice received intraperitoneal β-lg with Freund's adjuvant, followed by oral β-lg while receiving dextran sulphate sodium salt (DSS) in their drinking water (0.2% w/v). The immunized group without DSS and the groups receiving saline, oral β-lg, or DSS served as controls. Results: The study showed that the immunization effect was greater in mice with mild intestinal barrier dysfunction. Although DSS did not affect the mice's humoral response to β-lg, in combination with β-lg, it significantly altered their cellular response, affecting the induction and distribution of T cells in the inductive and peripheral tissues and the activation of immune mediators. Administration of β-lg to sensitized mice receiving DSS increased disease activity index (DAI) scores and pro-inflammatory cytokine activity, altered the distribution of claudins and zonulin 1 (ZO-1) in the colonic tissue, and negatively affected the balance and activity of the gut microbiota. Conclusions: The research model used appears attractive for studying food allergen sensitization, particularly in relation to the initial events leading to mucosal inflammation and the development of food hypersensitivity. [ABSTRACT FROM AUTHOR]

Objective: Spirulina (arthrospira platensis) is a cyanobacterium proven to have anti-inflammatory, antiviral, and antioxidant effects. However, the effect of highdose Spirulina supplementation on hospitalized adults with COVID-19 is currently unclear. This study aimed to evaluate the efficacy and safety of highdose Spirulina platensis for SARS-CoV-2 infection. Study Design: We conducted a randomized, controlled, open-label trial involving 189 patients with COVID-19 who were randomly assigned in a 1:1 ratio to an experimental group that received 15.2g of Spirulina supplement plus standard treatment (44 non-intensive care unit (non-ICU) and 47 ICU), or to a control group that received standard treatment alone (46 non-ICU and 52 ICU). The study was conducted over six days. Immune mediators were monitored on days 1, 3, 5, and 7. The primary outcome of this study was mortality or hospital discharge within seven days, while the overall discharge or mortality was considered the secondary outcome. Results: Within seven days, there were no deaths in the Spirulina group, while 15 deaths (15.3%) occurred in the control group. Moreover, within seven days, there was a greater number of patients discharged in the Spirulina group (97.7%) in non-ICU compared to the control group (39.1%) (HR, 6.52; 95% CI, 3.50 to 12.17). Overall mortality was higher in the control group (8.7% non-ICU, 28.8% ICU) compared to the Spirulina group (non-ICU HR, 0.13; 95% CI, 0.02 to 0.97; ICU, HR, 0.16; 95% CI, 0.05 to 0.48). In non-ICU, patients who received Spirulina showed a significant reduction in the levels of IL-6, TNF-β, IL-10, and IP-10 as intervention time increased. Furthermore, in ICU, patients who received Spirulina showed a significant decrease in the levels of MIP-1α and IL-6. IFN-γ levels were significantly higher in the intervention group in both ICU and non-ICU subgroups as intervention time increased. No side effects related to Spirulina supplements were observed during the trial. Conclusion: High-dose Spirulina supplements coupled with the standard treatment of COVID-19 may improve recovery and remarkably reduce mortality in hospitalized patients with COVID-19. [ABSTRACT FROM AUTHOR]

ObjectiveSpirulina (arthrospira platensis) is a cyanobacterium proven to have anti-inflammatory, antiviral, and antioxidant effects. However, the effect of high-dose Spirulina supplementation on hospitalized adults with COVID-19 is currently unclear. This study aimed to evaluate the efficacy and safety of high-dose Spirulina platensis for SARS-CoV-2 infection.Study DesignWe conducted a randomized, controlled, open-label trial involving 189 patients with COVID-19 who were randomly assigned in a 1:1 ratio to an experimental group that received 15.2g of Spirulina supplement plus standard treatment (44 non-intensive care unit (non-ICU) and 47 ICU), or to a control group that received standard treatment alone (46 non-ICU and 52 ICU). The study was conducted over six days. Immune mediators were monitored on days 1, 3, 5, and 7. The primary outcome of this study was mortality or hospital discharge within seven days, while the overall discharge or mortality was considered the secondary outcome.ResultsWithin seven days, there were no deaths in the Spirulina group, while 15 deaths (15.3%) occurred in the control group. Moreover, within seven days, there was a greater number of patients discharged in the Spirulina group (97.7%) in non-ICU compared to the control group (39.1%) (HR, 6.52; 95% CI, 3.50 to 12.17). Overall mortality was higher in the control group (8.7% non-ICU, 28.8% ICU) compared to the Spirulina group (non-ICU HR, 0.13; 95% CI, 0.02 to 0.97; ICU, HR, 0.16; 95% CI, 0.05 to 0.48). In non-ICU, patients who received Spirulina showed a significant reduction in the levels of IL-6, TNF-α, IL-10, and IP-10 as intervention time increased. Furthermore, in ICU, patients who received Spirulina showed a significant decrease in the levels of MIP-1α and IL-6. IFN-γ levels were significantly higher in the intervention group in both ICU and non-ICU subgroups as intervention time increased. No side effects related to Spirulina supplements were observed during the trial.ConclusionHigh-dose Spirulina supplements coupled with the standard treatment of COVID-19 may improve recovery and remarkably reduce mortality in hospitalized patients with COVID-19.Clinical Trial Registrationhttps://irct.ir/trial/54375, Iranian Registry of Clinical Trials number (IRCT20210216050373N1)

Tick-borne encephalitis (TBE) usually has a biphasic course which begins with unspecific febrile illness, followed by central nervous system involvement. Because TBE is not yet suspected during the initial phase, knowledge of early TBE pathogenesis is incomplete. Herein we evaluated laboratory and immune findings in the initial and second (meningoencephalitic) phase of TBE in 88 well-defined adult patients. Comparison of nine laboratory blood parameters in both phases of TBE revealed that laboratory abnormalities, consisting of low leukocyte and platelet counts and increased liver enzymes levels, were predominately associated with the initial phase of TBE and resolved thereafter. Assessment of 29 immune mediators in serum during the initial phase, and in serum and cerebrospinal fluid (CSF) during the second phase of TBE revealed highly distinct clustering patterns among the three groups. In the initial phase of TBE, the primary finding in serum was a rather heterogeneous immune response involving innate (CXCL11), B cell (CXCL13, BAFF), and T cell mediators (IL-27 and IL-4). During the second phase of TBE, growth factors associated with angiogenesis (GRO-α and VEGF-A) were the predominant characteristic in serum, whereas innate and Th1 mediators were the defining feature of immune responses in CSF. These findings imply that distinct immune processes play a role in the pathophysiology of different phases of TBE and in different compartments.

Background: The novel coronavirus disease 2019 (COVID-19) presents with complex pathophysiological effects in various organ systems. Following the COVID-19, there are shifts in biomarker and cytokine equilibrium associated with altered physiological processes arising from viral damage or aggressive immunological response. We hypothesized that high daily dose methylprednisolone improved the injury biomarkers and serum cytokine profiles in COVID-19 patients. Methods: Injury biomarker and cytokine analysis was performed on 50 SARS-Cov-2 negative controls and 101 hospitalized severe COVID-19 patients: 49 methylprednisolone-treated (MP group) and 52 placebo-treated serum samples. Samples from the treated groups collected on days D1 (pre-treatment) all the groups, D7 (2 days after ending therapy) and D14 were analyzed. Luminex assay quantified the biomarkers HMGB1, FABP3, myoglobin, troponin I and NTproBNP. Immune mediators (CXCL8, CCL2, CXCL9, CXCL10, TNF, IFN-γ, IL-17A, IL-12p70, IL-10, IL-6, IL-4, IL-2, and IL-1β) were quantified using cytometric bead array. Results: At pretreatment, the two treatment groups were comparable demographically. At pre-treatment (D1), injury biomarkers (HMGB1, TnI, myoglobin and FABP3) were distinctly elevated. At D7, HMGB1 was significantly higher in the MP group (p=0.0448) compared to the placebo group, while HMGB1 in the placebo group diminished significantly by D14 (p=0.0115). Compared to healthy control samples, several immune mediators (IL-17A, IL-6, IL-10, MIG, MCP-1, and IP-10) were considerably elevated at baseline (all p≤0.05). At D7, MIG and IP-10 of the MP-group were significantly lower than in the placebo-group (p=0.0431, p=0.0069, respectively). Longitudinally, IL-2 (MPgroup) and IL-17A (placebo-group) had increased significantly by D14. In placebo group, IL-2 and IL-17A continuously increased, as IL-12p70, IL-10 and IP-10 steadily decreased during follow-up. The MP treated group had IL-2, IFN-γ, IL-17A and IL-12p70 progressively increase while IL-1b and IL-10 gradually decreased towards D14. Moderate to strong positive correlations between chemokines and cytokines were observed on D7 and D14. Conclusion: These findings suggest MP treatment could ameliorate levels of myoglobin and FABP3, but appeared to have no impact on HMGB1, TnI and NTproBNP. In addition, methylprednisolone relieves the COVID-19 induced inflammatory response by diminishing MIG and IP-10 levels. Overall, corticosteroid (methylprednisolone) use in COVID-19 management influences the immunological molecule and injury biomarker profile in COVID-19 patients. [ABSTRACT FROM AUTHOR]

Anna Lisa Montemari,1 Melania Manco,2 Alessandro Giovanni Fiocchi,3 Manuela Bartoli,4 Francesco Facchiano,5 Claudio Tabolacci,5 Maria Scatigna,6 Fabiana Ciciriello,3 Federico Alghisi,3 Enza Montemitro,3 Rita Carsetti,7 Vincenzina Lucidi,3 Ersilia Vita Fiscarelli1 1UOS Cystic Fibrosis Diagnostic, UOC Microbiology and Immunology Diagnostic, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy; 2Research Area for Multifactorial Diseases, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy; 3Cystic Fibrosis Unit, Department of Pediatrics Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy; 4Department of Ophthalmology, Medical College of Georgia, Augusta University, Augusta, GA, USA; 5Department of Oncology and Molecular Medicine, Istituto Superiore Di Sanità, Rome, Italy; 6Department of Life, Health and Environmental Sciences, University of L’Aquila, L’Aquila, Italy; 7Diagnostic Immunology Unit, Department of Laboratories, B Cell Pathophysiology Unit, Immunology Research Area, Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyCorrespondence: Melania Manco, Bambino Gesù Children’s Hospital, IRCCS, piazza Sant’Onofrio 4, Rome, Italy, Tel +39 06 6859 2649, Fax +39 06 6859 2904, Email melania.manco@opbg.netObjective and Design: Cystic fibrosis-related diabetes (CFRD) is a severe complication associated with increased morbidity and mortality in cystic fibrosis (CF) patients. Extensive inflammatory state in CF leads to pancreas damage and insulin resistance with consequent altered glucose tolerance and CFRD development. The aim of the present study was to identify circulating levels of inflammatory markers specifically associated with impaired glucose tolerance (IGT) and overt CFRD in a sample of young adults with CF.Materials and Methods: Sixty-four CF outpatients, without evident active pulmonary exacerbation, infectious and autoimmune diseases, were enrolled in the study and the levels of 45 inflammatory serum mediators were measured through x magnetic bead panel multiplex technology.Results: Serum levels of PDGF-AA, CCL20/MIP3α, IFNα, CCL11/eotaxin, CXCL1/GROα, GMCSF, B7H1/PDL1, IL13, IL7, VEGF, and TGFα were all significantly (p< 0.05) elevated in patients according to glycemic status and directly correlated with glycated hemoglobin and C-reactive protein levels.Conclusion: Our findings suggest that increased levels of specific circulating inflammatory mediators are directly associated with impaired glucose tolerance in CF patients, thus, potentially implicating them in CFRD pathogenesis and warranting larger longitudinal studies to validate their monitoring as predictor of CFRD onset.Keywords: cystic fibrosis-related diabetes, cytokines, growth factors, immune mediators, impaired glucose tolerance, inflammation

BackgroundThe novel coronavirus disease 2019 (COVID-19) presents with complex pathophysiological effects in various organ systems. Following the COVID-19, there are shifts in biomarker and cytokine equilibrium associated with altered physiological processes arising from viral damage or aggressive immunological response. We hypothesized that high daily dose methylprednisolone improved the injury biomarkers and serum cytokine profiles in COVID-19 patients.MethodsInjury biomarker and cytokine analysis was performed on 50 SARS-Cov-2 negative controls and 101 hospitalized severe COVID-19 patients: 49 methylprednisolone-treated (MP group) and 52 placebo-treated serum samples. Samples from the treated groups collected on days D1 (pre-treatment) all the groups, D7 (2 days after ending therapy) and D14 were analyzed. Luminex assay quantified the biomarkers HMGB1, FABP3, myoglobin, troponin I and NTproBNP. Immune mediators (CXCL8, CCL2, CXCL9, CXCL10, TNF, IFN-γ, IL-17A, IL-12p70, IL-10, IL-6, IL-4, IL-2, and IL-1β) were quantified using cytometric bead array.ResultsAt pretreatment, the two treatment groups were comparable demographically. At pre-treatment (D1), injury biomarkers (HMGB1, TnI, myoglobin and FABP3) were distinctly elevated. At D7, HMGB1 was significantly higher in the MP group (p=0.0448) compared to the placebo group, while HMGB1 in the placebo group diminished significantly by D14 (p=0.0115). Compared to healthy control samples, several immune mediators (IL-17A, IL-6, IL-10, MIG, MCP-1, and IP-10) were considerably elevated at baseline (all p≤0.05). At D7, MIG and IP-10 of the MP-group were significantly lower than in the placebo-group (p=0.0431, p=0.0069, respectively). Longitudinally, IL-2 (MP-group) and IL-17A (placebo-group) had increased significantly by D14. In placebo group, IL-2 and IL-17A continuously increased, as IL-12p70, IL-10 and IP-10 steadily decreased during follow-up. The MP treated group had IL-2, IFN-γ, IL-17A and IL-12p70 progressively increase while IL-1β and IL-10 gradually decreased towards D14. Moderate to strong positive correlations between chemokines and cytokines were observed on D7 and D14.ConclusionThese findings suggest MP treatment could ameliorate levels of myoglobin and FABP3, but appeared to have no impact on HMGB1, TnI and NTproBNP. In addition, methylprednisolone relieves the COVID-19 induced inflammatory response by diminishing MIG and IP-10 levels. Overall, corticosteroid (methylprednisolone) use in COVID-19 management influences the immunological molecule and injury biomarker profile in COVID-19 patients.

Respiratory biomarkers have the potential to identify airway injury by revealing inflammatory processes within the respiratory tract. Currently, there are no respiratory biomarkers suitable for clinical use to identify patients that warrant further diagnostic work‐up, counseling, and treatment for toxic inhalant exposures or chronic airway disease. Using a novel, noninvasive method of sampling the nasal epithelial lining fluid, we aimed to investigate if nasal biomarker patterns could distinguish healthy nonsmoking adults from active smokers and those with chronic upper and lower airway disease in this exploratory study. We compared 28 immune mediators from healthy nonsmoking adults (n = 32), former smokers with COPD (n = 22), chronic rhinosinusitis (CRS) (n = 22), and smoking adults without airway disease (n = 13). Using ANOVA, multinomial logistic regressions, and weighted gene co‐expression network analysis (WGCNA), we determined associations between immune mediators and each cohort. Six mediators (IL‐7, IL‐10, IL‐13, IL‐12p70, IL‐15, and MCP‐1) were lower among disease groups compared to healthy controls. Participants with lower levels of IL‐10, IL‐12p70, IL‐13, and MCP‐1 in the nasal fluid had a higher odds of being in the COPD or CRS group. The cluster analysis identified groups of mediators that correlated with disease status. Specifically, the cluster of IL‐10, IL‐12p70, and IL‐13, was positively correlated with healthy and negatively correlated with COPD groups, and two clusters were correlated with active smoking. In this exploratory study, we preliminarily identified groups of nasal mucosal mediators that differed by airway disease and smoking status. Future prospective, age‐matched studies that control for medication use are needed to validate these patterns and determine if nasosorption has diagnostic utility for upper and lower airway disease or injury. [ABSTRACT FROM AUTHOR]

Severe injury is known to cause a systemic cytokine storm that is associated with adverse outcomes. However, a comprehensive assessment of the time-dependent changes in circulating levels of a broad spectrum of protein immune mediators and soluble immune mediator receptors in severely injured trauma patients remains uncharacterized. To address this knowledge gap, we defined the temporal and outcome-based patterns of 184 known immune mediators and soluble cytokine receptors in the circulation of severely injured patients. Proteomics (aptamer-based assay, SomaLogic, Inc) was performed on plasma samples drawn at 0, 24, and 72 hours (h) from time of admission from 150 trauma patients, a representative subset from the Prehospital Plasma during Air Medical Transport in Trauma Patients at Risk for Hemorrhagic Shock (PAMPer) trial. Patients were categorized into outcome groups including Early Non-Survivors (died within 72 h; ENS; n=38), Non-Resolvers (died after 72 h or required ≥7 days of intensive care; NR; n=78), and Resolvers (survivors that required < 7 days of intensive care; R; n=34), with low Injury Severity Score (ISS) patients from the Tranexamic Acid During Prehospital Transport in Patients at Risk for Hemorrhage After Injury (STAAMP) trial as controls. The major findings include an extensive release of immune mediators and cytokine receptors at time 0h that is more pronounced in ENS and NR patients. There was a selective subset of mediators elevated at 24 and 72 h to a greater degree in NR patients, including multiple cytokines and chemokines not previously described in trauma patients. These findings were validated in a quantitative fashion using mesoscale discovery immunoassays (MSD) from an external validation cohort (VC) of samples from 58 trauma patients matched for R and NR status. This comprehensive longitudinal description of immune mediator patterns associated with trauma outcomes provides a new level of characterization of the immune response that follows severe injury. [ABSTRACT FROM AUTHOR]

Severe injury is known to cause a systemic cytokine storm that is associated with adverse outcomes. However, a comprehensive assessment of the time-dependent changes in circulating levels of a broad spectrum of protein immune mediators and soluble immune mediator receptors in severely injured trauma patients remains uncharacterized. To address this knowledge gap, we defined the temporal and outcome-based patterns of 184 known immune mediators and soluble cytokine receptors in the circulation of severely injured patients. Proteomics (aptamer-based assay, SomaLogic, Inc) was performed on plasma samples drawn at 0, 24, and 72 hours (h) from time of admission from 150 trauma patients, a representative subset from the Prehospital Plasma during Air Medical Transport in Trauma Patients at Risk for Hemorrhagic Shock (PAMPer) trial. Patients were categorized into outcome groups including Early Non-Survivors (died within 72 h; ENS; n=38), Non-Resolvers (died after 72 h or required ≥7 days of intensive care; NR; n=78), and Resolvers (survivors that required < 7 days of intensive care; R; n=34), with low Injury Severity Score (ISS) patients from the Tranexamic Acid During Prehospital Transport in Patients at Risk for Hemorrhage After Injury (STAAMP) trial as controls. The major findings include an extensive release of immune mediators and cytokine receptors at time 0h that is more pronounced in ENS and NR patients. There was a selective subset of mediators elevated at 24 and 72 h to a greater degree in NR patients, including multiple cytokines and chemokines not previously described in trauma patients. These findings were validated in a quantitative fashion using mesoscale discovery immunoassays (MSD) from an external validation cohort (VC) of samples from 58 trauma patients matched for R and NR status. This comprehensive longitudinal description of immune mediator patterns associated with trauma outcomes provides a new level of characterization of the immune response that follows severe injury.

• Fungi-derived molecules affect mast cell response. • β-glucans and mannan serve as potent mast cell chemoattractants. • Fungi cell wall molecules activate mast cells to degranulate and generate mediators. • The activity of mast cells induced by fungal molecules ​is mediated through PRRs. Mast cells (MCs) are the first immune cell type that can contact with the external environment, where they may rapidly sense the presence of pathogens. These cells are directly involved in innate defense through their ability to pathogen destruction by several mechanisms and the pattern recognition receptors (PRRs) they express. Several studies have focused on the aspects of MC responses to bacterial and viral pathogens or their specific components and the role of those cells in antibacterial or antiviral defense mechanisms. However, to date, the knowledge of the influence of various fungi-derived molecules on MC activity is primarily based on limited data. Thus, this study aims to compare the effect of the major fungi cell wall-associated antigens, i.e., two β-(1,3)-glucans: zymosan - β-(1,3)-glucan containing mannan and chitin, and curdlan - purified linear model β-(1,3)-glucan as well as mannan on peritoneal MC activity. In particular, the potency of various fungal cell wall components to induce MC migration, degranulation, and generation and/or release of de novo-synthesized mediators/cytokines/chemokines was analyzed. The most striking result to emerge from the data is that MC activation differs depending on the fungal stimuli. Our study outlines that components of the inner layer of the fungi cell wall - β-glucans, i.e., zymosan and curdlan, are more potent stimulators of MC activity compared to mannan. On this note, the data described here may provide a foundation for further studying the role of MC in antifungal immunity and be helpful for a better understanding of host-pathogenic fungi interactions. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Fibromyalgia (FM) is a complex chronic pain condition. Its symptoms are nonspecific, and to date, no objective test exists to confirm FM diagnosis. Potential objective measures include the circulating levels of blood biomarkers. This systematic review and meta-analysis aim to review studies assessing blood biomarkers' levels in patients with FM compared with healthy controls. We systematically searched the PubMed, MEDLINE, EMBASE, and PsycINFO databases. Fifty-four studies reporting the levels of biomarkers in blood in patients with FM were included. Data were extracted, and the methodological quality was assessed independently by 2 authors. The methodological quality of 9 studies (17%) was low. The results of most studies were not directly comparable given differences in methods and investigated target immune mediators. Thus, data from 40 studies only were meta-analyzed using a random-effects model. The meta-analysis showed that patients with FM had significantly lower levels of interleukin-1 β and higher levels of IL-6, IL-8, tumor necrosis factor-alpha, interferon gamma, C-reactive protein, and brain-derived neurotrophic factor compared with healthy controls. Nevertheless, this systematic literature review and meta-analysis could not support the notion that these blood biomarkers are specific biomarkers of FM. Our literature review, however, revealed that these same individual biomarkers may have the potential role of identifying underlying pathologies or other conditions that often coexist with FM. Future research is needed to evaluate the potential clinical value for these biomarkers while controlling for the various confounding variables. [ABSTRACT FROM AUTHOR]

In the present study, the levels of serum and airway soluble chemokines, pro-inflammatory/regulatory cytokines, and growth factors were quantified in critically ill COVID-19 patients (total n=286) at distinct time points (D0, D2-6, D7, D8-13 and D>14-36) upon Intensive Care Unit (ICU) admission. Augmented levels of soluble mediators were observed in serum from COVID-19 patients who progress to death. An opposite profile was observed in tracheal aspirate samples, indicating that systemic and airway microenvironment diverge in their inflammatory milieu. While a bimodal distribution was observed in the serum samples, a unimodal peak around D7 was found for most soluble mediators in tracheal aspirate samples. Systems biology tools further demonstrated that COVID-19 display distinct eccentric soluble mediator networks as compared to controls, with opposite profiles in serum and tracheal aspirates. Regardless the systemic-compartmentalized microenvironment, networks from patients progressing to death were linked to a pro-inflammatory/growth factor-rich, highly integrated center. Conversely, patients evolving to discharge exhibited networks of weak central architecture, with lower number of neighborhood connections and clusters of pro-inflammatory and regulatory cytokines. All in all, this investigation with robust sample size landed a comprehensive snapshot of the systemic and local divergencies composed of distinct immune responses driven by SARS-CoV-2 early on severe COVID-19. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) affects more than 1% of children, and there is no viable pharmacotherapeutic agent to treat the core symptoms of ASD. Studies have shown that children with ASD show changes in their levels of immune response molecules. Our previous studies have shown that ASD is more common in children with folate receptor autoantibodies. We also found that children with ASD have abnormal gut immune function, which was characterized by a significant increase in the content of immunoglobulin A and an increase in gut-microbiota-associated epitope diversity. These studies suggest that the immune mechanism plays an important role in the occurrence of ASD. The present study aims to systematically assess gene mutations in immune mediators in patients with ASD. We collected genetic samples from 72 children with ASD (2–12 years old) and 107 healthy controls without ASD (20–78 years old). We used our previously-designed immune gene panel, which can capture cytokine and receptor genes, the coding regions of MHC genes, and genes of innate immunity. Target region sequencing (500×) and bioinformatics analytical methods were used to identify variants in immune response genes associated with patients with ASD. A total of 4 rare variants were found to be associated with ASD, including HLA-B: p.A93G, HLA-DQB1: p.S229N, LILRB2: p.R322H, and LILRB2: c.956-4C>T. These variants were present in 44.44% (32/72) of the ASD patients and were detected in 3.74% (4/107) of the healthy controls. We expect these genetic variants will serve as new targets for the clinical genetic assessment of ASD, and our findings suggest that immune abnormalities in children with ASD may have a genetic basis. [ABSTRACT FROM AUTHOR]

Immunostimulants play an important role in the treatment of immunodeficiency. Macrophages are the first line in our immune defense system and play a critical role in the immune response. Therefore, finding new and better substances to induce an immune response by activating macrophages is an attractive research topic, especially in the fields of immunopharmacology and cancer prevention. Keratinocytes actively crosstalk with immune cells during wound repair, so enhancing the function of keratinocytes is also an important part of improving immunity. Beta-glucans are naturally occurring polysaccharides, consisting of d-glucose monomers linked by beta-glycosidic bonds. Several studies have investigated the immunomodulatory effects of beta-glucan, such as its anti-inflammatory and antibacterial properties. However, the use of yeast cell wall glucan has been limited because it is not soluble in water. In this study, we produced low-molecular-weight water-soluble yeast glucan (WSY glucan) and confirmed various aspects of its immune-enhancing effect. The structure of the beta-(1→3) and (1→6) bonds of WSY glucan were confirmed by nuclear magnetic resonance spectroscopy (1H-NMR) analysis. Our results showed that treatment with WSY glucan significantly and dose-dependently induced the production of inflammatory mediators (prostaglandin E2 (PGE2) and nitric oxide (NO)) and pro-inflammatory cytokines (tumor necrosis factor (TNF)-α and interleukin (IL)-6) in macrophages. In addition, WSY glucan treatment showed changes in the morphological structure of the macrophages and promoted phagocytic activity of the macrophages and wound healing in keratinocytes. Based on these results, WSY glucan is considered as a potential candidate for the treatment of diseases related to the weakening of the immune system without the limitation of insolubility.

(1) Background: Sepsis is a life-threatening condition caused by an abnormal host response to infection that produces altered physiological responses causing tissue damage and can result in organ dysfunction and, in some cases, death. Although sepsis is characterized by a malfunction of the immune system leading to an altered immune response and immunosuppression, the high complexity of the pathophysiology of sepsis requires further investigation to characterize the immune response in sepsis and septic shock. (2) Methods: This study analyzes the immune-related responses occurring during the early stages of sepsis by comparing the amounts of cytokines, immune modulators and other endothelial mediators of a control group and three types of severe patients: critically ill non-septic patients, septic and septic shock patients. (3) Results: We showed that in the early stages of sepsis the innate immune system attempts to counteract infection, probably via neutrophils. Conversely, the adaptive immune system is not yet fully activated, either in septic or in septic shock patients. In addition, immunosuppressive responses and pro-coagulation signals are active in patients with septic shock. (4) Conclusions: The highest levels of IL-6 and pyroptosis-related cytokines (IL-18 and IL-1α) were found in septic shock patients, which correlated with D-dimer. Moreover, endothelial function may be affected as shown by the overexpression of adhesion molecules such as s-ICAM1 and E-Selectin during septic shock. [ABSTRACT FROM AUTHOR]

Astrocyte heterogeneity is a rapidly evolving field driven by innovative techniques. Inflammatory astrocytes, one of the first described subtypes of reactive astrocytes, are present in a variety of neurodegenerative diseases and may play a role in their pathogenesis. Moreover, genetic and therapeutic targeting of these astrocytes ameliorates disease in several models, providing support for advancing the development of astrocyte-specific disease modifying therapies. This review aims to explore the methods and challenges of identifying inflammatory astrocytes, the role these astrocytes play in neurological disorders, and future directions in the field of astrocyte heterogeneity.

Background: Allergies are on the rise globally, with an enormous impact on affected individuals’ quality of life as well as health care resources. They cause a wide range of symptoms, from slightly inconvenient to potentially fatal immune reactions. While allergies have been described and classified phenomenologically, there is an unmet need for easily accessible biomarkers to stratify the severity of clinical symptoms. Furthermore, biomarkers marking the success of specific immunotherapy are urgently needed. Objectives: Plasma extracellular vesicles (pEV) play a role in coordinating the immune response and may be useful future biomarkers. A pilot study on differences in pEV content was carried out between patients with type I allergy, suffering from rhinoconjunctivitis with or without asthma, and voluntary non-allergic donors. Methods: We examined pEV from 38 individuals (22 patients with allergies and 16 controls) for 38 chemokines, cytokines, and soluble factors using high-throughput data mining approaches. Results: Patients with allergies had a distinct biomarker pattern, with 7 upregulated (TNF-alpha, IL-4, IL-5, IL-6, IL-17F, CCL2, and CCL17) and 3 downregulated immune mediators (IL-11, IL-27, and CCL20) in pEV compared to controls. This reduced set of 10 factors was able to discriminate controls and allergic patients better than the total array. Conclusions: The content of pEV showed potential as a target for biomarker research in allergies. Plasma EV, which are readily measurable via blood test, may come to play an important role in allergy diagnosis. In this proof-of-principle study, it could be shown that pEV's discriminate patients with allergies from controls. Further studies investigating whether the content of pEVs may predict the severity of allergic symptoms or even the induction of tolerance to allergens are needed.

Recurrent abdominal pain (RAP) is a common medically unexplained symptom among children worldwide. However, the biological mechanisms behind the development of functional and behavioral symptoms and changes in blood markers have not been well explored. This study aimed to assess changes in the concentrations of inflammatory markers, including cytokines and tryptophan catabolites, in the serum of children with RAP compared to those with subclinical infections. Children with RAP but without organic diseases were included, and those with asymptomatic intestinal parasitic infections were used as a subclinical infection cohort. Blood samples were collected and used to measure the cytokine profile using Multiplex Immunoassay and tryptophan catabolites using high performance liquid chromatography. Children with RAP showed significantly higher concentrations of serum tumor necrotic factor-α, p

Astrocyte heterogeneity is a rapidly evolving field driven by innovative techniques. Inflammatory astrocytes, one of the first described subtypes of reactive astrocytes, are present in a variety of neurodegenerative diseases and may play a role in their pathogenesis. Moreover, genetic and therapeutic targeting of these astrocytes ameliorates disease in several models, providing support for advancing the development of astrocyte-specific disease modifying therapies. This review aims to explore the methods and challenges of identifying inflammatory astrocytes, the role these astrocytes play in neurological disorders, and future directions in the field of astrocyte heterogeneity. [ABSTRACT FROM AUTHOR]

Recurrent abdominal pain (RAP) is a common medically unexplained symptom among children worldwide. However, the biological mechanisms behind the development of functional and behavioral symptoms and changes in blood markers have not been well explored. This study aimed to assess changes in the concentrations of inflammatory markers, including cytokines and tryptophan catabolites, in the serum of children with RAP compared to those with subclinical infections. Children with RAP but without organic diseases were included, and those with asymptomatic intestinal parasitic infections were used as a subclinical infection cohort. Blood samples were collected and used to measure the cytokine profile using Multiplex Immunoassay and tryptophan catabolites using high performance liquid chromatography. Children with RAP showed significantly higher concentrations of serum tumor necrotic factor-α, p <0.05, but lower concentrations of IL-10, p <0.001, IL-6, p <0.001 and brain-derived neurotrophic factors (BDNF) p <0.01. In addition, a significant increase in the metabolite of the kynurenine pathway, 3-hydroxyanthranilic acid (3-HAA) p <0.01, a significant decrease in the concentrations of anthranilic acid (AA) p <0.001, together with an increased ratio of serum 3-HAA to AA (3-HAA/AA) p <0.001, was found in this cohort. These findings indicate the significant activation of the immune system and presence of inflammation in children with RAP than those with subclinical parasitic infections. Moreover, children with RAP tested with the Strengths and Difficulties Questionnaire (SDQ) , displayed high psychological problems though these SDQ scores were not statistically associated with measured cytokines and kynurenine metabolites. We however could hypothesize that the pro-inflammatory state together with concomitant low concentrations of BDNF in those children with RAP could play a role in psychological stress and experiencing medically unexplained symptoms. [ABSTRACT FROM AUTHOR]

Mast cells take part in host defense against microorganisms as they are numerous at the portal of infection, exert several essential mechanisms of pathogen destruction, and they express pattern recognition receptors. Accumulating evidence indicates that these cells are involved in the control and clearance of bacterial, viral, or parasitic infections, but much less is known about their contribution in defense against fungi. The study was aimed to establish whether mannan, which comprises an outermost layer and major structural constituent of the fungal cell wall, may directly stimulate tissue mast cells to the antifungal response. Our findings indicate that mannan activates mast cells isolated from the rat peritoneal cavity to initiate the proinflammatory response. We found that mannan stimulates mast cells to release histamine and to generate cysteinyl leukotrienes, cytokines (IFN‐γ, GM‐CSF, TNF), and chemokines (CCL2, CCL3). It also increased the mRNA expression of various cytokines/chemokines. We also documented that mannan strongly activates mast cells to generate reactive oxygen species and serves as a potent chemoattractant for these cells. Furthermore, we established that mannan‐induced activity of mast cells is mediated via TLR4 with the involvement of the spleen tyrosine kinase molecule. Taking together, our results clearly support the idea that mast cells act as sentinel cells and crucially determine the course of the immune response during fungal infection. Additionally, presented data on IgE‐coated mast cells suggest that exposure to fungal mannan could influence the severity of IgE‐dependent diseases, including allergic ones. [ABSTRACT FROM AUTHOR]

Mast cells (MCs) play an essential role in host defense, primarily because of their location, their ability to pathogen destruction via several mechanisms, and the pattern recognition receptors they express. Even though most data is available regarding MC activation by various bacteria- or virus-derived molecules, those cells' activity in response to constituents associated with fungi is not recognized enough. Our research aimed to address whether Saccharomyces cerevisiae-derived zymosan, i.e., β-(1,3)-glucan containing mannan particles, impacts MC activity aspects. Overall, the obtained results indicate that zymosan has the potential to elicit a pro-inflammatory response of rat peritoneal MCs. For the first time ever, we provided evidence that zymosan induces fully mature MC migration, even in the absence of extracellular matrix (ECM) proteins. Moreover, the zymosan-induced migratory response of MCs is almost entirely a result of directional migration, i.e., chemotaxis. We found that zymosan stimulates MCs to degranulate and generate lipid mediators (cysLTs), cytokines (IFN-α, IFN-β, IFN-γ, GM-CSF, TNF), and chemokine (CCL2). Zymosan also upregulated mRNA transcripts for several cytokines/chemokines with pro-inflammatory/immunoregulatory activity. Moreover, we documented that zymosan activates MCs to produce reactive oxygen species (ROS). Lastly, we established that the zymosan-induced MC response is mediated through activation of the Dectin-1 receptor. In general, our results strongly support the notion that MCs contribute to innate antifungal immunity and bring us closer to elucidate their role in host-pathogenic fungi interactions. Besides, provided findings on IgE-sensitized MCs appear to indicate that exposure to fungal zymosan could affect the severity of IgE-dependent disorders, including allergic ones. [ABSTRACT FROM AUTHOR]

Human pericardial fluid (PF) is a rich reservoir of biologically active markers. The acellular compartment of PF can drive cardiac fibroblast activity in vitro. This process is mediated through the transforming growth factor-β pathway. Of clinical importance, the PF of patients with coronary artery disease has an increased profibrotic capacity compared with the PF of patients without coronary artery disease., Competing Interests: Dr Fatehi Hassanabad was supported by a Canadian Institutes of Health Research–Vanier Canada Graduate Scholarship, a Killam Foundation Doctoral Award, an Alberta Innovates: Health Solutions Doctoral Scholarship, and a Kertland Family Doctoral Award. A Canadian Institutes of Health Research Grant supports Drs Dundas and Fedak. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Chemical allergy can manifest into allergic contact dermatitis and asthma and the importance of skin sensitization in both of these diseases is increasingly being recognized. Given the unique characteristics of chemical allergy, coupled with the distinct immunological microenvironment of the skin research is still unraveling the mechanisms through which sensitization and elicitation occur. This review first describes the features of chemical sensitization and the known steps that must occur to develop a chemical allergy. Next, the unique immunological properties of the skin - which may influence chemical sensitization - are highlighted. Additionally, mediators involved with the development of allergy are reviewed, starting with early ones - including the properties of haptens, skin integrity, the microbiome, the inflammasome, and toll-like receptors (TLR). Novel cellular mediators of chemical sensitization are highlighted, including innate lymphoid cells, mast cells, T-helper (TH) cell subsets, and skin intrinsic populations including γδ T-cells and resident memory T-cells. Finally, this review discusses two epigenetic mechanisms that can influence chemical sensitization, microRNAs and DNA methylation. Overall, this review highlights recent research investigating novel mediators of chemical allergy that are present in the skin. It also emphasizes the need to further explore these mediators to gain a better understanding of what makes a chemical an allergen, and how best to prevent the development of chemical-induced allergic diseases.

The new coronavirus (COVID‐19) was first reported in Wuhan in China, on 31 December 2019. COVID‐19 is a new virus from the family of coronaviruses that can cause symptoms ranging from a simple cold to pneumonia. The virus is thought to bind to the angiotensin‐converting enzyme 2, as a well‐known mechanism to enter the cell. It then transfers its DNA to the host in which the virus replicates the DNA. The viral infection leads to severe lack of oxygen, lung oxidative stress because of reactive oxygen species generation, and overactivation of the immune system by activating immune mediators. The purpose of this review is to elaborate on the more precise mechanism(s) to manage the treatment of the disease. Regarding the mechanisms of the virus action, the suggested pharmacological and nutritional regimens have been described. [ABSTRACT FROM AUTHOR]

(1) Background: Sepsis is a life-threatening condition caused by an abnormal host response to infection that produces altered physiological responses causing tissue damage and can result in organ dysfunction and, in some cases, death. Although sepsis is characterized by a malfunction of the immune system leading to an altered immune response and immunosuppression, the high complexity of the pathophysiology of sepsis requires further investigation to characterize the immune response in sepsis and septic shock. (2) Methods: This study analyzes the immune-related responses occurring during the early stages of sepsis by comparing the amounts of cytokines, immune modulators and other endothelial mediators of a control group and three types of severe patients: critically ill non-septic patients, septic and septic shock patients. (3) Results: We showed that in the early stages of sepsis the innate immune system attempts to counteract infection, probably via neutrophils. Conversely, the adaptive immune system is not yet fully activated, either in septic or in septic shock patients. In addition, immunosuppressive responses and pro-coagulation signals are active in patients with septic shock. (4) Conclusions: The highest levels of IL-6 and pyroptosis-related cytokines (IL-18 and IL-1α) were found in septic shock patients, which correlated with D-dimer. Moreover, endothelial function may be affected as shown by the overexpression of adhesion molecules such as s-ICAM1 and E-Selectin during septic shock.

Oesophageal adenocarcinoma (OAC) is an exemplar model of obesity-associated cancer. Previous work in our group has demonstrated that overweight/obese OAC patients have better responses to neoadjuvant therapy, but the underlying mechanisms are unknown. Unravelling the immune–metabolic signatures of adipose tissue may provide insight for this observation. We hypothesised that different metabolic pathways predominate in visceral (VAT) and subcutaneous adipose tissue (SAT) and inflammatory secretions will differ between the fat depots. Real-time ex vivo metabolic profiles of VAT and SAT from 12 OAC patients were analysed. These samples were screened for the secretion of 54 inflammatory mediators, and data were correlated with patient body composition. Oxidative phosphorylation (OXPHOS) was significantly higher in VAT when compared to SAT. OXPHOS was significantly higher in the SAT of patients receiving neoadjuvant treatment. VEGF-A, VEGF-C, P1GF, Flt-1, bFGF, IL-15, IL-16, IL-17A, CRP, SAA, ICAM-1, VCAM-1, IL-2, IL-13, IFN-γ, and MIP-1β secretions were significantly higher from VAT than SAT. Higher levels of bFGF, Eotaxin-3, and TNF-α were secreted from the VAT of obese patients, while higher levels of IL-23 and TARC were secreted from the SAT of obese patients. The angiogenic factors, bFGF and VEGF-C, correlated with visceral fat area. Levels of OXPHOS are higher in VAT than SAT. Angiogenic, vascular injury and inflammatory cytokines are elevated in VAT versus SAT, indicating that VAT may promote inflammation, linked to regulating treatment response.

Immune and inflammatory cascades may play multiple roles in ovarian cancer. We aimed to identify relationships between expression of immune and inflammatory mediators and patient outcomes. We interrogated differential gene expression of 44 markers and marker combinations (n = 1,978) in 1,656 ovarian carcinoma patient tumors, alongside matched 5-year overall survival (OS) data in silico. Using machine learning methods, we investigated whether genomic expression of these 44 mediators can discriminate between malignant and non-malignant tissues in 839 ovarian cancer and 115 non-malignant ovary samples. We furthermore assessed inflammation markers in 289 ovarian cancer patients’ sera in the Swedish Apolipoprotein MOrtality-related RISk (AMORIS) cohort. Expression of the 44 mediators could discriminate between malignant and non-malignant tissues with at least 96% accuracy. Higher expression of classical Th1, Th2, Th17, anti-parasitic/infection and M1 macrophage mediator signatures were associated with better OS. Contrastingly, inflammatory and angiogenic mediators, CXCL-12, C-reactive protein (CRP) and platelet-derived growth factor subunit A (PDGFA) were negatively associated with OS. Of the serum inflammatory markers in the AMORIS cohort, women with ovarian cancer who had elevated levels of haptoglobin (≥1.4 g/L) had a higher risk of dying from ovarian cancer compared to those with haptoglobin levels

Post-operative adhesions affect patients undergoing all types of surgeries. They are associated with serious complications, including higher risk of morbidity and mortality. Given increased hospitalization, longer operative times, and longer length of hospital stay, post-surgical adhesions also pose a great financial burden. Although our knowledge of some of the underlying mechanisms driving adhesion formation has significantly improved over the past two decades, literature has yet to fully explain the pathogenesis and etiology of post-surgical adhesions. As a result, finding an ideal preventative strategy and leveraging appropriate tissue engineering strategies has proven to be difficult. Different products have been developed and enjoyed various levels of success along the translational tissue engineering research spectrum, but their clinical translation has been limited. Herein, we comprehensively review the agents and products that have been developed to mitigate post-operative adhesion formation. We also assess emerging strategies that aid in facilitating precision and personalized medicine to improve outcomes for patients and our healthcare system.

Chemical allergy can manifest into allergic contact dermatitis and asthma and the importance of skin sensitization in both of these diseases is increasingly being recognized. Given the unique characteristics of chemical allergy, coupled with the distinct immunological microenvironment of the skin research is still unraveling the mechanisms through which sensitization and elicitation occur. This review first describes the features of chemical sensitization and the known steps that must occur to develop a chemical allergy. Next, the unique immunological properties of the skin - which may influence chemical sensitization - are highlighted. Additionally, mediators involved with the development of allergy are reviewed, starting with early ones - including the properties of haptens, skin integrity, the microbiome, the inflammasome, and toll-like receptors (TLR). Novel cellular mediators of chemical sensitization are highlighted, including innate lymphoid cells, mast cells, T-helper (TH) cell subsets, and skin intrinsic populations including γδ T-cells and resident memory T-cells. Finally, this review discusses two epigenetic mechanisms that can influence chemical sensitization, microRNAs and DNA methylation. Overall, this review highlights recent research investigating novel mediators of chemical allergy that are present in the skin. It also emphasizes the need to further explore these mediators to gain a better understanding of what makes a chemical an allergen, and how best to prevent the development of chemical-induced allergic diseases. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to determine if an association exists between basal levels of stress and immune mediators and military physical performance among Canadian Armed Forces members (CAF). Methods: Blood samples from 219 CAF members (86 women and 133 men), were analysed for levels of cortisol, C-reactive protein (CRP), Adiponectin, INF-γ, TNF-α, IL-1β, IL-2, IL-6, IL-8 and IL-18. Grip strength, aerobic capacity and performance on six military physical performance tests (sandbag fortification, escape to cover, picking and digging, picket and wire carry, stretcher carry and vehicle extrication) were also assessed. A composite score for total performance was computed, based on rank scores from the six tasks. Results: The results from the linear regression analysis showed that higher CRP values were associated with lower total performance scores (slope -23.0,p≤0.05), a slower picking and digging time (slope 45.75,p≤0.05), lower aerobic capacity (slope -71.81,p≤0.05) and shorter plank time (slope -21.82,p≤0.05). A positive association between IL-2 values and grip strength was also observed (slope 20.83,p≤0.05). Adiponectin values were positively associated with plank time (slope 21.42,p≤0.05), but negatively associated with grip strength (slope -8.27,p≤0.05). Conclusion: The results from this study suggest that high levels of immune mediators (like CRP) could be a marker of decreased military physical performance. [ABSTRACT FROM AUTHOR]

Patrizia Fuschiotti Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Abstract: Systemic sclerosis (SSc or scleroderma) is a progressive and highly debilitating autoimmune disorder characterized by inflammation, vasculopathy, and extensive fibrosis. SSc is highly heterogeneous in its clinical presentation, extent and severity of skin and internal organ involvement, and clinical course and has the highest fatality rate among connective tissue diseases. While clinical outcomes have improved in recent years, no current therapy is able to reverse or slow the natural progression of SSc, a reflection of its complex pathogenesis. Although activation of the immune system has long been recognized, the mechanisms responsible for the initiation of autoimmunity and the role of immune effector pathways in the pathogenesis of SSc remain incompletely understood. This review summarizes recent progress in disease pathogenesis with particular focus on the immunopathogenetic mechanisms of SSc. Keywords: scleroderma, immune mediators, inflammation, autoimmunity

The article comments on a study which evaluated the diagnostic utility of CXCL13, a B-cell chemoattractant, in lyme neuroborreliosis (LNB). A comparison between the presentations of LNB in North American and European patients is discussed. The primary criteria for the diagnosis of LNB include the presence of clinical signs and symptoms suggestive of LNB, cerebrospinal fluid (CSF) pleocytosis and borrelia intrathecal antibody synthesis (ITAbs). The diagnostic benefits of CXCL13 are described.

Background: Individuals in the geriatric age range are more prone than younger individuals to convert their partial thickness thermal burns into full thickness injuries. We hypothesized that this often observed clinical phenomenon is strongly related to differential local injury responses mediated by the immune system.Materials& Methods: Skin samples from areas with partial thickness thermal burns were obtained during routine excision and grafting procedures between post burn days 2-6. Tissue samples were grouped by age ranges with young patients defined as <30 years of age or aged patients defined as >65. Formalin fixed samples were used to confirm depth of burn injury and companion sections were homogenized for multiplex analysis using a Luminex platform. Immunohistochemical staining was used to quantify total macrophage numbers as well as the M1 and M2 subpopulations.Results: Our analysis includes samples derived from 11 young subjects (mean age=23) and 3 aged subjects (mean age=79.2). Our initial survey of analytes examined 31 cytokines/chemokines. Twelve were excluded from consideration as they were present in concentrations either above or below the optimal detection range. Two analytes emerged as candidate molecules with significant differences between the young and the aged patient responses to burn injury. EGF levels were on average 21.69pg/ml in young vs 14.87pg/ml in aged (p=0.032). RANTES/CCL5 levels were on average 14.86pg/ml in young vs 4.26pg/ml in aged (p=0.026). Elevated macrophage numbers were present within wounds of younger patients compared to the old (p<0.01), with a higher concentration of the M1 type in the elderly (p>0.05).Conclusion: Our study has identified at least 2 well known cytokines, CCL5 (RANTES) and EGF, which are differentially regulated in response to burn injury by young versus aged burn victims. Evidence suggests that a proinflammatory environment can explain the high conversion rate from partial to full thickness burns. Our data suggest the need for future studies at the point of injury (cutaneous targets) that may be modulated by post burn release of cytokines/chemokines. [ABSTRACT FROM AUTHOR]

Introduction: Periodontitis is highly complex and multifactorial disease. The reasons for periodontal illnesses are microorganism. The human oral cavity harbors a significant and persistently developing heap of microbial species. The natural cooperations between the host and organisms decide the seriousness of the ailment. Experimental evidences confirm that certain bacterial strains in periodontal environment can induce gingival tissue inflammation and bone destruction. The pathogenesis of periodontal illnesses is intervened by the fiery reaction to microscopic organisms in the dental biofilm. Materials and Methods: The study population consisted of aggressive periodontitis (n = 3), juvenile periodontitis (n = 3), and healthy individuals (n = 3) with no systemic or oral diseases. Determination of interleukin (IL)-17, and neutrophil infiltration and monocyte clustering were determined. Results: Neutrophil infiltration or disruption exhibited by adult periodontitis was greater when compared to juvenile periodontitis. There was an increased expression of IL-17 in juvenile periodontitis when compared to adult periodontitis. Conclusion: In light of the outcomes, it can be reasoned that the neutrophil infiltration in adult periodontitis is greater when compared to juvenile periodontitis whereas the IL-17 expression is greater in juvenile periodontitis on comparison with healthy and adult periodontitis. [ABSTRACT FROM AUTHOR]

This prospective study aimed to address changes in inflammatory response between different aged populations of patients who sustained burn and inhalation injury. Plasma and bronchoalveolar lavage (BAL) samples were collected from 104 patients within 15 h of their estimated time of burn injury. Clinical variables, laboratory parameters, and immune mediator profiles were examined in association with clinical outcomes. Older patients were at higher odds for death after burn injury (odds ratio (OR) = 7.37 per 10 years, p = 0.004). In plasma collected within 15 h after burn injury, significant increases in the concentrations of interleukin 1 receptor antagonist (IL-1RA), interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 6 (IL-6), granulocyte colony-stimulating factor (G-CSF), interferon-gamma-induced protein 10 (IP-10) and monocyte chemoattractant protein 1 (MCP-1) (p < 0.05 for all) were observed in the ≥ 65 group. In the BAL fluid, MCP-1 was increased three-fold in the ≥ 65 group. This study suggests that changes in certain immune mediators were present in the older cohort, in association with in-hospital mortality. [ABSTRACT FROM AUTHOR]

Introduction: Periostin is a matricellular protein expressed by many tissues. Its release may be enhanced, among others, through mechanical stimulation of muscles and bones as well as by cytokines of allergic inflammation. Objectives: Our aim was to assess periostin levels in serum and exhaled breath condensate (EBC) of professional athletes, asthmatics and healthy controls. We also sought to determine whether acute treadmill exercise influences serum and EBC periostin. Methods: Study groups included 9 competitive swimmers, 10 mild-to-moderate asthmatics and 7 healthy controls. Athletes were assessed twice (in- and off-training period) while asthmatics and controls in one time-point. Data on demographics, allergy symptoms and exercise load were acquired through Allergy Questionnaire for Athletes (AQUA) and International Physical Activity Questionnaire (IPAQ). Serum and EBC were collected before and after treadmill exercise challenge. Results: Baseline serum periostin in swimmers during training period was significantly higher (5- to 7-fold) than in asthmatics (P = .01) and controls (P < .05). In EBC, lowest periostin levels were seen in athletes in-training as compared with offtraining period (P < .01) and with asthmatics (P < .03). Acute bout of exercise did not induce significant changes neither in serum nor in EBC periostin in any group. Conclusion: Increased serum, but not EBC, periostin levels in competitive athletes are probably because of permanently increased exercise load leading to stimulation, injury and regeneration of musculoskeletal tissues. Periostin may be considered marker of long-term exercise overload after confirmation in larger groups. [ABSTRACT FROM AUTHOR]

Leptospirosis remains one of the most widespread zoonotic diseases caused by spirochetes of the genus Leptospira , which accounts for high morbidity and mortality globally. Leptospiral infections are often found in tropical and subtropical regions, with people exposed to contaminated environments or animal reservoirs are at high risk of getting the infection. Leptospirosis has a wide range of clinical manifestations with non-specific signs and symptoms and often misdiagnosed with other acute febrile illnesses at early stage of infection. Despite being one of the leading causes of zoonotic morbidity worldwide, there is still a gap between pathogenesis and human immune responses during leptospiral infection. It still remains obscure whether the severity of the infection is caused by the pathogenic properties of the Leptospira itself, or it is a consequence of imbalance host immune factors. Hence, in this review, we seek to summarize the past and present milestone findings on the biomarkers of host immune response aspects during human leptospiral infection, including cytokine and other immune mediators. A profound understanding of the interlink between virulence factors and host immune responses during human leptospirosis is imperative to identify potential biomarkers for diagnostic and prognostic applications as well as designing novel immunotherapeutic strategies in future. [ABSTRACT FROM AUTHOR]

Background & Aims:Malfunctions of enteric neurons are believed to play an important role in the pathophysiology of irritable bowel syndrome (IBS). Our aim was to investigate whether neuronal activity in biopsies from IBS patients is altered in comparison to healthy controls (HC).Methods:Activity of human submucous neurons in response to electrical nerve stimulation and local application of nicotine or a mixture of histamine, serotonin, tryptase and TNF-α (IBS-cocktail) was recorded in biopsies from 17 HC and 35 IBS patients with the calcium-sensitive-dye Fluo-4 AM. The concentrations of the mediators resembeled those found in biopsy supernatants or blood. Neuronal activity in guinea-pig submucous neurons was studied with the voltage-sensitive-dye di-8-ANEPPS. Results:Activity in submucous ganglia in response to nicotine or electrical nerve stimulation was not different between HC and IBS patients (P=0.097 or P=0.448). However, the neuronal response after application of the IBS-cocktail was significantly decreased (P=0.039) independent of whether diarrhea (n=12), constipation (n=5) or bloating (n=5) was the predominant symptom. In agreement with this we found that responses of submucous ganglia conditioned by overnight incubation with IBS mucosal biopsy supernatant to spritz application of this supernatant was significantly reduced (P=0.019) when compared to incubation with HC supernatant.Conclusion:We demonstrated for the first time reduced neuronal responses in mucosal IBS biopsies to an IBS mediator cocktail. While excitability to classical stimuli of enteric neurons was comparable to HC, the activation by the IBS-cocktail was decreased. This was very likely due to desensitization to mediators constantly released by mucosal and immune cells in the gut wall of IBS patients.

Sertoli cells provide appropriate mitogens, differentiation factors and sources of energy for developing germ cells throughout the lifetime of males, and protect these germ cells from harmful agents and from the host's own immune system. Therefore, reductions in the rate and quality of spermatogenesis caused by nanoparticulate titanium dioxide (nano-TiO2) may be closely involved in the immunoregulation of Sertoli cells. However, the underlying mechanism of this response is still unclear. To address this issue, we used mouse primary cultured Sertoli cells to examine the toxic effects of nano-TiO2 via alterations in morphology, cell viability, and activation of the TAM/TLR3 signal pathway. The results demonstrated that nano-TiO2 could cross the cytomembrane into the cytoplasm or nucleus, decrease Sertoli cell viability, damage morphology (such as elongated fusiform, cellular and nuclear shrinkage) and induce the expression of various immune mediators and inflammatory cytokines, including TLR3(+0.31-fold to +0.81-fold), IL-lβ(+0.33-fold to +5.0-fold), NF-κB(+0.22-fold to +3.65-fold), IL-6(+0.47-fold to +3.53-fold), TNF-α(+0.14-fold to +2.44-fold), IFN-α(+0.17-fold to +2.27-fold), and IFN-β(+0.09-fold to +2.29-fold), and suppress the expression of Tyro3(−9.33% to −61.93%), Axl(−19.03% to −60.67%), Mer(−8.04% to −59.16%), and IκB(−34.35% to −86.59%) in primary cultured Sertoli cells. These results suggest that testicular innate immune responses to pathogens caused by nano-TiO2 may be involved in the regulatory mechanisms of TAM/TLR3 signaling in testicular Sertoli cells. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 198-208, 2017. [ABSTRACT FROM AUTHOR]

Progressive multifocal leukoemcephalopathy (PML) is a fatal demyelinating disease caused by the human neurotropic JC virus (JCV). JCV infects the majority of the human population during childhood and establishes a latent/persistent life-long infection. The virus reactivates under immunosuppressive conditions by unknown mechanisms, resulting in productive infection of oligodendrocytes in the central nervous system (CNS). Given the fact that the natural occurrence of PML is strongly associated with immunosuppression, the functional and molecular interaction between glial cells and neuroimmune signaling mediated by soluble immune mediators is likely to play a major role in reactivation of JCV and the progression of the lytic viral life cycle leading to the development of PML. In order to explore the effect of soluble immune mediators secreted by peripheral blood mononuclear cells (PBMCs) on JCV transcription, primary human fetal glial (PHFG) cells were treated with conditioned media from PBMCs. We observed a strong suppression of JCV early as well as late gene transcription in cells treated with conditioned media from induced PBMCs. Using a variety of virological and molecular biological approaches, we demonstrate that immune mediators secreted by PBMCs induce the expression of SRSF1, a strong inhibitor of JCV gene expression, and inhibit the replication of JCV. Our results show that downregulation of SRSF1 in glial cells overcomes the suppression of JCV gene expression and its replication mediated by soluble immune mediators. These findings suggest the presence of a novel immune signaling pathway between glial cells and PBMCs that may control JCV gene expression during the course of viral reactivation. [ABSTRACT FROM AUTHOR]

Background We recently demonstrated a dual effect of breastfeeding with increased risk of eczema and decreased risk of wheezing in early childhood by increasing breastfeeding length. We hypothesize that immune mediators in breast milk could explain such association either through a direct effect or as a surrogate marker of maternal immune constitution. Objective To investigate the possible association between cytokine and chemokine levels in breast milk and development of eczema and recurrent wheeze during early childhood. Methods Levels of 19 pro-inflammatory and immunoregulatory cytokines and chemokines were measured in 223 breast milk samples from mothers in the Copenhagen Prospective Study on Asthma in Childhood2000 (COPSAC) high-risk birth cohort. Eczema and recurrent wheeze at the age of 0-3 years were prospectively diagnosed by COPSAC physicians adherent to predefined validated algorithms. Association analyses were performed by Cox regression adjusting for potential confounding factors and by multivariable principal component analysis. Results Increased IL-1β in breast milk (≥ 0.7 pg/mL) was associated with more than a halved risk of eczema before age three ( aHR = 0.41; 95% CI = 0.24-0.68; P < 0.001), which remained significant after false discovery rate adjustment ( P = 0.008). The principal component analysis confirmed that a mediator pattern dominated by high levels of IL-1β, IL-17A, and CCL17 and low levels of CXCL1 and TSLP in breast milk protected against eczema ( aHR = 0.82; 95% CI = 0.68-0.98; P = 0.03). No associations were observed for recurrent wheeze. Conclusions and Clinical Relevance Elevated breast milk IL-1β level was associated with decreased risk of early childhood eczema suggesting either a direct protective effect of IL-1β or IL-1b acting as a proxy for a healthy maternal immune system protecting high-risk offspring from eczema. [ABSTRACT FROM AUTHOR]

Cerebral ischemia, neuroinflammation, immune cells, immunotherapy, peripheral immune system, immune mediators Keywords: cerebral ischemia; neuroinflammation; peripheral immune system; immune cells; immune mediators; immunotherapy EN cerebral ischemia neuroinflammation peripheral immune system immune cells immune mediators immunotherapy 1 2 2 12/29/21 20211224 NES 211224 Cerebral ischemia or ischemic stroke (IS) is a leading cause of death worldwide, only behind cardiac ischemia. Fangxi Liu et al. reviewed the cross-talk between the brain and the immune system after stroke and pointed out that the beneficial or detrimental effects of peripheral immune cells on the ischemic brain depend on the time course of stroke. [Extracted from the article]

Background and Aims: Malfunctions of enteric neurons are believed to play an important role in the pathophysiology of irritable bowel syndrome (IBS). Our aim was to investigate whether neuronal activity in biopsies from IBS patients is altered in comparison to healthy controls (HC). Methods: Activity of human submucous neurons in response to electrical nerve stimulation and local application of nicotine or a mixture of histamine, serotonin, tryptase, and TNF-a (IBS-cocktail) was recorded in biopsies from 17 HC and 35 IBS patients with the calcium-sensitive-dye Fluo-4 AM. The concentrations of the mediators resembeled those found in biopsy supernatants or blood. Neuronal activity in guinea-pig submucous neurons was studied with the voltage-sensitive-dye di-8-ANEPPS. Results: Activity in submucous ganglia in response to nicotine or electrical nerve stimulation was not different between HC and IBS patients (P = 0.097 or P = 0.448). However, the neuronal response after application of the IBS-cocktail was significantly decreased (P = 0.039) independent of whether diarrhea (n = 12), constipation (n = 5) or bloating (n = 5) was the predominant symptom. In agreement with this we found that responses of submucous ganglia conditioned by overnight incubation with IBS mucosal biopsy supernatant to spritz application of this supernatant was significantly reduced (P = 0.019) when compared to incubation with HC supernatant. Conclusion: We demonstrated for the first time reduced neuronal responses in mucosal IBS biopsies to an IBS mediator cocktail. While excitability to classical stimuli of enteric neurons was comparable to HC, the activation by the IBS-cocktail was decreased. This was very likely due to desensitization to mediators constantly released by mucosal and immune cells in the gut wall of IBS patients. [ABSTRACT FROM AUTHOR]

Resistance to erythropoietin (EPO) affects a significant number of anaemic patients with end-stage renal disease. Previous reports suggest that inflammation is one of the major independent predictors of EPO resistance, and the effects of EPO treatment on inflammatory mediators are not well established. The aim of this study was to investigate EPO-induced modification to gene expression in primary cultured leucocytes. Microarray experiments were performed on primed ex vivo peripheral blood mononuclear cells (PBMCs) and treated with human EPO-α. Data suggested that EPO-α modulated genes involved in cell movement and interaction in primed PBMCs. Of note, EPO-α exerts anti-inflammatory effects inhibiting the expression of pro-inflammatory cytokine IL-8 and its receptor CXCR2; by contrast, EPO-α increases expression of genes relating to promotion of inflammation encoding for IL-1β and CCL8, and induces de novo synthesis of IL-1α, CXCL1 and CXCL5 in primed cells. The reduction in MAPK p38-α activity is involved in modulating both IL-1β and IL-8 expression. Unlike the induction of MAPK, Erk1/2 activity leads to upregulation of IL-1β, but does not affect IL-8 expression and release. Furthermore, EPO-α treatment of primed cells induces the activation of caspase-1 upstream higher secretion of IL-1β, and this process is not dependent on caspase-8 activation. In conclusion, our findings highlight new potential molecules involved in EPO resistance and confirm the anti-inflammatory role for EPO, but also suggest a plausible in vivo scenario in which the positive correlation found between EPO resistance and elevated levels of some pro-inflammatory mediators is due to treatment with EPO itself.