IL-1ra Concentrations Research Articles

Elevated Plasma IL-6 Coincides with Activation of STAT3 in PBMC After Acute Resistance Exercise.

Changes in plasma concentrations of anti-inflammatory cytokines, such as interleukin-6 (IL-6) and IL-10, after acute resistance exercise (RE) have been widely explored. Whether observed changes in plasma cytokine concentration correspond to the activation of anti-inflammatory signaling pathways in immune cells after acute RE is unknown. This study aimed to determine if changes in plasma cytokines after acute RE resulted in the activation of anti-inflammatory signaling pathways in peripheral blood mononuclear cells (PBMC). Healthy young males (N = 16; age = 23.5 ± 2.7 yr; BMI = 22.4 ± 1.7 kg·m-2) participated in a single session of whole-body RE (4 sets of 4 different exercises at 70% 1-repetition maximum with the last set to failure) and a sedentary control (CON) condition in a randomized crossover design. Blood samples were collected at several time points before and after the exercise bout. Higher plasma IL-6, IL-10, and IL-1 RA concentrations were observed after RE compared with CON. Phosphorylation of STAT3 and protein expression of SOCS3 in PBMC were increased in RE compared with CON. The elevation of plasma IL-6, but not IL-10, coincided with the activation of STAT3 signaling in PBMC. These results highlight a potential mechanism by which RE may exert anti-inflammatory actions in circulating immune cells.

Seasonal Comparative Analysis of Follicular Interleukin Concentration and Expression of IL1RII, IL4 and IL1RA in Cystic Follicles Versus Normal Preovulatory Follicles in Buffalo

Seasonal Comparative Analysis of Follicular Interleukin Concentration and Expression of IL1RII, IL4 and IL1RA in Cystic Follicles Versus Normal Preovulatory Follicles in Buffalo

Distinct dynamics of mRNA LNPs in mice and nonhuman primates revealed by in vivo imaging

The characterization of vaccine distribution to relevant tissues after in vivo administration is critical to understanding their mechanisms of action. Vaccines based on mRNA lipid nanoparticles (LNPs) are now being widely considered against infectious diseases and cancer. Here, we used in vivo imaging approaches to compare the trafficking of two LNP formulations encapsulating mRNA following intramuscular administration: DLin-MC3-DMA (MC3) and the recently developed DOG-IM4. The mRNA formulated in DOG-IM4 LNPs persisted at the injection site, whereas mRNA formulated in MC3 LNPs rapidly migrated to the draining lymph nodes. Furthermore, MC3 LNPs induced the fastest increase in blood neutrophil counts after injection and greater inflammation, as shown by IL-1RA, IL-15, CCL-1, and IL-6 concentrations in nonhuman primate sera. These observations highlight the influence of the nature of the LNP on mRNA vaccine distribution and early immune responses.

Rapid decrease in IL-1Ra and IP-10 plasma levels following tuberculosis treatment initiation

ObjectivesMonitoring tools that could provide quick predictions of tuberculosis (TB) treatment outcomes are urgently needed. Here, we assessed whether the evolution of selected biomarkers of innate immunity may help monitoring TB treatment response within 2 weeks of treatment initiation. MethodsANRS12394-LILAC-TB was a proof-of-concept prospective study: adults with a rifampicin-susceptible TB who are HIV-negative and HIV-infected documented by a positive Xpert MTB/RIF test were enrolled in Cambodia and Côte d'Ivoire. Plasma concentrations of interleukin-1 receptor antagonist (IL-1Ra), interferon-γ–induced protein-10 and clusters of differentiation (CD) (scavenging CD163) were measured by commercial enzyme-linked immunosorbent assay kits. A Wilcoxon test for paired data was used for longitudinal comparisons. ResultsA total of 55 patients were enrolled (women: 31%, median age: 37 years; median CD4 count in the 10 of 13 participants with HIV: 53 cells/mm3). Overall, 83% were considered in TB treatment success. Compared with baseline, the IL-1Ra plasma levels significantly decreased as soon as week (W) 1, independent of HIV status (−71% in HIV-positive vs −33% in HIV-negative; P <0.001). The IP-10 plasma levels significantly decreased at W1 and W2 compared with baseline (P <0.0001); however, that decrease was less marked in participants with HIV. ConclusionsOur findings suggest that measuring IL-1Ra plasma levels with a standard enzyme-linked immunosorbent assay technique at baseline and then 1 week after TB treatment onset could help clinicians to quickly assess TB treatment response.

Inflammatory Protein Signatures as Predictive Disease-Specific Markers for Non-Alcoholic Steatohepatitis (NASH).

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic disease worldwide, consisting of a broad spectrum of diseases such as simple steatosis (NAFL), non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. Hepatic inflammation plays a key role in the pathophysiology of NAFLD. Inflammatory mediators such as cytokines and chemokines are considered as contributing factors to NAFLD development and progression. In the present study, we aimed to investigate the inflammatory protein signatures as predictive disease-specific markers for non-alcoholic fatty liver disease (NAFLD). This cross-sectional study included healthy control (n = 64), NAFL (n = 109), and NASH (n = 60) human subjects. Serum concentrations of various cytokines and chemokines were evaluated using sensitive multiplex assays. We used principal component analysis (PCoA) to reveal distinct differences in the levels of cytokines and chemokines between each of the study groups. Further, a random forest classification model was developed to identify the panel of markers that could predict diseases. The protein-protein network analysis was performed to determine the various signaling pathways associated with the disease-specific panel of markers. Serum concentrations of TNF-α, IL-1β, IL-1ra, G-CSF, PDGF-BB, MCP-1, MIP-1a, MIP-1b, RANTES, eotaxin, IL-8 and IP-10 were significantly increased in NASH group as compared to control group. Furthermore, serum concentrations of IL-9 and IL-13 were significantly lower in the NASH group, whereas IL-2 levels were significantly decreased in the NAFL group when compared to the control group. PCoA results demonstrated statistically significant differences in cytokines and chemokines between each of the study groups (PERMANOVA p = 0.001; R2 = 0.102). RANTES, IL-1ra, MIP-1b, IL-2, and G-CSF could differentiate the NAFL group from the controls; G-CSF, IL-1ra, TNF-α, RANTES, and IL-9 could differentiate the NASH group from the controls; and G-CSF, IL-9, IL-13, eotaxin, and TNF- α could differentiate the NASH group from the NAFL group. Our protein-protein network revealed that these markers are involved in cytokine-cytokine receptor interaction, Th1 and Th2 cell differentiation, TNF, chemokine, JAK/STAT, P13K/Akt, TLR, NOD-like receptor, NF-kB, and adipocytokine signaling pathways which might be responsible for disease pathogenesis.Our study findings revealed a set of distinct cytokine and chemokine markers and they might be considered as biomarkers in distinguishing NASH from NAFL. Future multicentre studies with larger sample size are recommended to determine the potential utility of these panels of markers.

Similar immune responses to alpha1-oleate and Bacillus Calmette-Guérin treatment in patients with bladder cancer.

The molecular content of urine is defined by filtration in the kidneys and by local release from tissues lining the urinary tract. Pathological processes and different therapies change the molecular composition of urine and a variety of markers have been analyzed in patients with bladder cancer. The response to BCG immunotherapy and chemotherapy has been extensively studied and elevated urine concentrations of IL-1RA, IFN-α, IFN-γ TNF-α, and IL-17 have been associated with improved outcome. In this study, the host response to intravesical alpha 1-oleate treatment was characterized in patients with non-muscle invasive bladder cancer by proteomic and transcriptomic analysis. Proteomic profiling detected a significant increase in multiple cytokines in the treatment group compared to placebo. The innate immune response was strongly activated, including IL-1RA and pro-inflammatory cytokines in the IL-1 family (IL-1α, IL-1β, IL-33), chemokines (MIP-1α, IL-8), and interferons (IFN-α2, IFN-γ). Adaptive immune mediators included IL-12, Granzyme B, CD40, PD-L1, and IL-17D, suggesting broad effects of alpha 1-oleate treatment on the tumor tissues. The cytokine response profile in alpha 1-oleate treated patients was similar to that reported in BCG treated patients, suggesting a significant overlap. A reduction in protein levels at the end of treatment coincided with inhibition of cancer-related gene expression in tissue biopsies, consistent with a positive treatment effect. Thus, in addition to killing tumor cells and inducing cell detachment, alpha 1-oleate is shown to activate a broad immune response with a protective potential.

Cord Blood-Derived Multipotent Stem Cells Ameliorate in Vitro/in Vivo Alloreactive Responses, and This Effect Is Associated with Exosomal Microvesicles in Vitro

Human cord blood derived-multipotent stem cells (CB-SCs) have been found to have immunomodulatory capabilities that can result in inhibition of immune activation. Clinically, when used to interact with apheresed peripheral blood mononuclear cells (PBMCs) before reinfusion, they can counteract inflammation and restore immune balance in patients with autoimmune diseases, including alopecia areata and type 1 diabetes. The present study aimed to explore the potential application of CB-SCs to control donor alloreactive responses involved in allogeneic hematopoietic cell transplantation, which often results in acute graft-versus-host disease (GVHD). Phenotypically, we demonstrated that CB-SCs express CD45, CD11b, and CD9 markers on the cell surface; express Oct3/4, a transcription factor for embryonic stem cells; are negative for CD3, CD14, and CD34 expression; and have low expression of HLA-DR. In an allogeneic mixed lymphocyte culture (MLC) using human CD4 T cell enriched PBMCs and allogeneic myeloid derived dendritic cells, direct coculture with CB-SCs decreased CD4 T cell proliferation and activation, as evidenced by a marked decrease in the expression of the late activation markers CD25 and HLA-DR and a reduction of the PKH26 cell proliferation membrane lipophilic marker. Cytokine profiling of MLC supernatants revealed decreased concentrations of inflammatory proteins, including IFN-γ, IL-17, IL-13, IL-2, IL-6, and MIP1-α, along with marked increases in IL-1RA, IP-10, and MCP-1 concentrations in the presence of CB-SCs. Furthermore, transwell MLC experiments revealed that a soluble component was partially responsible for the immunomodulatory effects of CB-SCs. In this regard, exosomal microvesicles (EVs) positive for CD9, CD63, and CD81 were found in CB-SC-derived, ultrafiltered, and ultracentrifuged culture supernatants. CB-SC-EVs inhibited T cell proliferation in allogeneic MLC, suggesting a potential mode of action in allogeneic responses. Finally, CB-SCs were evaluated for their cellular therapy potential in vivo and found to ameliorate the development of GVHD responses in a xenogeneic human PBMC-induced NSG mouse model. Taken together, our results indicate that CB-SCs can directly and indirectly attenuate alloreactive CD4 T cell activation and proliferation in vitro with a potentially related EV mode of action and may have potential as a cellular therapy to control donor T cell-mediated GVHD responses in vivo.

Patients with higher numbers of allergies have lower levels of anti-inflammatory cytokines and increased pain at the time of ACL reconstruction

BackgroundSynovial fluid biomarkers are well studied indicators of inflammation and healing in the setting of orthopedic injuries. However, it has not been studied if patients with one or more allergies have a difference in the concentrations of synovial fluid inflammatory cytokines compared to patients without allergies. The purpose of the current study is to analyze the concentration of 10 pro- and anti-inflammatory cytokines in the synovial fluid of isolated ACL injury patients with and without at least one allergy. Study DesignRetrospective Case-Control. MethodsA database of patients who underwent surgery for isolated ACL injury between September 2011 and July 2023 was analyzed. All patients had SF aspirated from the operative knee prior to the surgical incision and the concentrations of pre- and anti-inflammatory biomarkers were quantified. From this cohort, 24 patients were identified to have allergies by chart review. These patients were matched 1:1 to 24 patients without allergies based on age and sex. ResultsThere were no significant differences between the allergy and no allergy cohorts with respect to age (28.5 ± 10.3 vs. 29.5 ± 8.9, p = 0.76) and sex (70.8 % female vs. 70.8 % female, p = 1.00). The allergy cohort had a decreased concentration of TIMP-1 (492.41 ± 616.20 ng/mL vs. 1041.48 ± 942.04 ng/mL, p = 0.03) and IL-1Ra (101.70 ± 93.37 pg/mL vs. 359.94 ± 399.77 pg/mL, p = 0.01) compared to patients without allergies. A linear regression analysis found a significant association between increasing number of patients reported allergies and decreasing concentration of TIMP-1 (β = -231.59, p = 0.03) and IL-1Ra (β = -71.69p = 0.03) concentrations when controlling for age and sex. Finally, the allergy cohort was found to have a significantly higher value for the VAS pain scale at the time of surgery (26.84 ± 24.73 vs. 7.37 ± 10.98, p < 0.01) compared to those without an allergy. ConclusionPatients undergoing ACL reconstruction with at least one allergy were found to have decreased concentrations of the anti-inflammatory cytokines TIMP-1 and IL-1Ra in their synovial fluid compared to those without allergies on the day of surgery. Furthermore, an increase in total number of allergies was found to be an associated with a decrease in TIMP-1 and IL-1Ra levels. Finally, the allergy cohort also had a higher value for the VAS pain scale at the time of surgery, implicating the role of a patient’s innate immune system to their biologic and symptomatic response to injury.

Heterogeneity in Neutrophil Extracellular Traps from Healthy Human Subjects.

Neutrophil extracellular traps (NETs), a key component of early defense against microbial infection, are also associated with tissue injury. NET composition has been reported to vary with some disease states, but the composition and variability of NETs across many healthy subjects provide a critical comparison that has not been well investigated. We evaluated NETs from twelve healthy subjects of varying ages isolated from multiple blood draws over a three-and-one-half-year period to delineate the variability in extracellular DNA, protein, enzymatic activities, and susceptibility to protease inhibitors. We calculated correlations for NET constituents and loss of human bronchial epithelial barrier integrity, measured by transepithelial electrical resistance, after NET exposure. We found that although there was some variability within the same subject over time, the mean NET total DNA, dsDNA, protein, LDH, neutrophil elastase (NE), and proteinase 3 (PR3) in isolated NETs were consistent across subjects. NET serine protease activity varied considerably within the same donor from day to day. The mean NET cathepsin G and MPO were significantly different across donors. IL-8 > IL-1RA > G-CSF were the most abundant cytokines in NETs. There was no significant difference in the mean concentration or variability of IL-8, IL-1RA, G-CSF, IL-1α, IL-1β, or TNF-α in different subjects' NETs. NET DNA concentration was correlated with increased NET neutrophil elastase activity and higher NET IL-1RA concentrations. The mean reduction in protease activity by protease inhibitors was significantly different across donors. NET DNA concentration correlated best with reductions in the barrier integrity of human bronchial epithelia. Defining NET concentration by DNA content correlates with other NET components and reductions in NET-driven epithelial barrier dysfunction, suggesting DNA is a reasonable surrogate measurement for these complex structures in healthy subjects.

Local Postoperative Graft Inflammation in Pancreas Transplant Patients With Early Graft Thrombosis

Background. Graft thrombosis is the main cause of early graft loss following pancreas transplantation, and is more frequent in pancreas transplant alone (PTA) compared with simultaneous pancreas-kidney (SPK) recipients. Ischemia-reperfusion injury during transplantation triggers a local thromboinflammatory response. We aimed to evaluate local graft inflammation and its potential association with early graft thrombosis. Methods. In this observational study, we monitored 67 pancreas-transplanted patients using microdialysis catheters placed on the pancreatic surface during the first postoperative week. We analyzed 6 cytokines, interleukin-1 receptor antagonist (IL-1ra), IL-6, IL-8, interferon gamma-induced protein 10 (IP-10), macrophage inflammatory protein 1β (MIP-1β), IL-10, and the complement activation product complement activation product 5a (C5a) in microdialysis fluid. We compared the dynamic courses between patients with pancreas graft thrombosis and patients without early complications (event-free) and between PTA and SPK recipients. Levels of the local inflammatory markers, and plasma markers C-reactive protein, pancreas amylase, and lipase were evaluated on the day of thrombosis diagnosis compared with the first week in event-free patients. Results. IL-10 and C5a were not detectable. Patients with no early complications (n = 34) demonstrated high IL-1ra, IL-6, IL-8, IP-10, and MIP-1β concentrations immediately after surgery, which decreased to steady low levels during the first 2 postoperative days (PODs). Patients with early graft thrombosis (n = 17) demonstrated elevated IL-6 (P = 0.003) concentrations from POD 1 and elevated IL-8 (P = 0.027) concentrations from POD 2 and throughout the first postoperative week compared with patients without complications. IL-6 (P &lt; 0.001) and IL-8 (P = 0.003) were higher on the day of thrombosis diagnosis compared with patients without early complications. No differences between PTA (n = 35) and SPK (n = 32) recipients were detected. Conclusions. Local pancreas graft inflammation was increased in patients experiencing graft thrombosis, with elevated postoperative IL-6 and IL-8 concentrations, but did not differ between PTA and SPK recipients. Investigating the relationship between the local cytokine response and the formation of graft thrombosis warrants further research.

Unveiling COVID-19 Secrets: Harnessing Cytokines as Powerful Biomarkers for Diagnosis and Predicting Severity.

In coronavirus disease (COVID-19), inflammation takes center stage, with a cascade of cytokines released, contributing to both inflammation and lung damage. The objective of this study is to identify biomarkers for diagnosing and predicting the severity of COVID-19. Cytokine levels were determined in the serum from venous blood samples collected from 100 patients with COVID-19 and 50 healthy controls. COVID-19 patients classified based on the Modified Early Warning (MEWS) score. Cytokine concentrations were determined with a multiplex ELISA kit (Bio-Plex Pro™ Human Cytokine Screening Panel). The concentrations of all analyzed cytokines were elevated in the serum of COVID-19 patients relative to the control group, but no significant differences were observed in interleukin-9 (IL-9) and IL-12 p70 levels. In addition, the concentrations of IL-1α, IL-1β, IL-1ra, IL-2Rα, IL-6, IL-12 p40, IL-18, and tumor necrosis factor alpha (TNFα) were significantly higher in symptomatic patients with accompanying pneumonia without respiratory failure (stage 2) than in asymptomatic/mildly symptomatic patients (stage 1). The study revealed that IL-1ra, IL-2Rα, IL-6, IL-8, IL-12 p40, IL-16, and IL-18 levels serve as potential diagnostic biomarkers in COVID-19 patients. Furthermore, elevated IL-1α levels proved to be valuable in assessing the severity of COVID-19.

Flow Cytometric Analysis of Macrophages and Cytokines Profile in the Bronchoalveolar Lavage Fluid in Patients with Lung Cancer.

Macrophages play an important role in the suppression and activation of immune anti-cancer response, but little is known about dominant macrophage phenotype in the lung cancer environment, evaluated by bronchoalveolar lavage fluid (BALF). The aim of this study was to characterize macrophages in BALF from a lung affected by cancer (cBALF) and a healthy lung (hBALF) of the same patient regarding their individual macrophage polarization and selected cytokines profile. A total of 36 patients with confirmed lung cancer were investigated. Macrophages markers: CD206 CD163 CD80 CD86 CD40 CD45, Arginase-1, and CD68 were evaluated by flow cytometry. Cytokines (IL-1 RA, IL-6, IL-10, TNF-α, IL-1β, IL-12, IL-23, and TGF-β) profile was analyzed. There was higher median proportion of macrophages in Cbalf than in Hbalf. The population of macrophages presented immunophenotype: Ccd68+bright CD206+bright CD163+bright CD80+ CD86+ CD40+bright CD45+ cArginase+. We observed some trends in the expression of the analyzed antigens in clBALF and hlBLAF. The highest concentrations of IL-1RA and IL-6 were in Cbalf and Hbalf supernatant. There were the correlations between pro- and anti-inflammatory cytokines. The findings showed that macrophages include a diverse and plastic group with the presence of different antigens and cytokines, and determining the target phenotype is a complex and variable process.

The imbalance of circulating pro-inflammatory cytokines interleukin-12 and interferon gamma and anti-inflammatory cytokine interleukin-1ra in chronic insomnia disorder

A growing body of literature suggests that cytokines can play an important role in chronic insomnia disorder (CID); however, the underlying mechanisms are still unknown. Here we show that serum levels of pro-inflammatory mediators including IL-12, IFN-γ and ICAM-1 are elevated in CID group when compared with healthy controls, and that the REM sleep duration diminishes with increased concentrations of IL-12 and IFN-γ in individuals with CID. Furthermore, we find that lowered serum concentration of IL-1ra is negatively correlated with severity of insomnia in CID group. These data add to the evidence that the imbalance of circulating pro-inflammatory mediators IL-12, IFN-γ, and ICAM-1 and anti-inflammatory cytokine IL-1ra is important in CID pathogenesis.

Serum Cytokines and Growth Factors in Subjects with Type 1 Diabetes: Associations with Time in Ranges and Glucose Variability.

The detrimental effect of hyperglycemia and glucose variability (GV) on target organs in diabetes can be implemented through a wide network of regulatory peptides. In this study, we assessed a broad panel of serum cytokines and growth factors in subjects with type 1 diabetes (T1D) and estimated associations between concentrations of these molecules with time in ranges (TIRs) and GV. One hundred and thirty subjects with T1D and twenty-seven individuals with normal glucose tolerance (control) were included. Serum levels of 44 cytokines and growth factors were measured using a multiplex bead array assay. TIRs and GV parameters were derived from continuous glucose monitoring. Subjects with T1D compared to control demonstrated an increase in concentrations of IL-1β, IL-1Ra, IL-2Rα, IL-3, IL-6, IL-7, IL-12 p40, IL-16, IL-17A, LIF, M-CSF, IFN-α2, IFN-γ, MCP-1, MCP-3, and TNF-α. Patients with TIR ≤ 70% had higher levels of IL-1α, IL-1β, IL-6, IL-12 p70, IL-16, LIF, M-CSF, MCP-1, MCP-3, RANTES, TNF-α, TNF-β, and b-NGF, and lower levels of IL-1α, IL-4, IL-10, GM-CSF, and MIF than those with TIR > 70%. Serum IL-1β, IL-10, IL-12 p70, MCP-1, MCP-3, RANTES, SCF, and TNF-α correlated with TIR and time above range. IL-1β, IL-8, IL-10, IL-12 p70, MCP-1, RANTES, MIF, and SDF-1α were related to at least one amplitude-dependent GV metric. In logistic regression models, IL-1β, IL-4, IL-10, IL-12 p70, GM-CSF, HGF, MCP-3, and TNF-α were associated with TIR ≤ 70%, and MIF and PDGF-BB demonstrated associations with coefficient of variation values ≥ 36%. These results provide further insight into the pathophysiological effects of hyperglycemia and GV in people with diabetes.

A pilot study to determine the optimal dose of scAAVIL-1ra in a large animal model of post-traumatic osteoarthritis

Gene therapy approaches using adeno-associated viral vectors have been successfully tested in the equine post-traumatic osteoarthritis (PTOA) model. Owing to differences in the levels of transgene expression and adverse tissue reactions observed in published studies, we sought to identify a safe therapeutic dose of scAAVIL-1ra in an inflamed and injured joint that would result in improved functional outcomes without any adverse events. scAAVIL-1ra was delivered intra-articularly over a 100-fold range, and horses were evaluated throughout and at the end of the 10-week study. A dose-related increase in IL-1ra levels with a decrease in PGE2 levels was observed, with the peak IL-1ra concentration being observed 7 days post-treatment in all groups. Perivascular infiltration with mononuclear cells was observed within the synovial membrane of the joint treated with the highest viral dose of 5 × 1012 vg, but this was absent in the lower-dosed joints. The second-highest dose of scAAVeqIL-1ra 5 × 1011 vg demonstrated elevated IL-1ra levels without any cellular response in the synovium. Taken together, the data suggest that the 10-fold lower dose of 5 × 1011vg scAAVIL-1ra would be a safe therapeutic dose in an equine model of PTOA.

Interleukin-1 Receptor Antagonist, Mode of Analgesia and Risk of Cesarean Delivery After Onset of Labor: A Mendelian Randomization Analysis

(Br J Anaesth. 2022;128:89–97) Inflammation during labor can cause a host of complications that can in turn lead to emergency cesarean delivery due to increased risks to both mother and child. The body has natural responses to inflammation, one of which is the release of an anti-inflammatory cytokine, an interleukin-1 receptor antagonist (IL-1ra). The gene that encodes the expression of IL-1ra has 2 upstream alleles that increase mRNA expression and IL-1ra concentration. Previously in similar situations where genes have been identified and associated, Mendelian randomization techniques have been able to show causal relationships between the genes and observable outcomes.

Comparison of the cytokine responses to acute strength exercise between oral contraceptive users and naturally cycling women

PurposeCytokines are released as part of an inflammatory reaction in response to strength exercise to initiate muscle repair and morphological adaptations. Whether hormonal fluctuations induced by the menstrual cycle or oral contraceptives affect inflammatory responses to strength exercise remains unknown. Therefore, we aimed to compare the response of cytokines after acute strength exercise in naturally menstruating women and oral contraceptive users.MethodsNaturally menstruating women (MC, n = 13, 24 ± 4 years, weekly strength training: 4.3 ± 1.7 h) and women using a monophasic combined pill (> 9 months) (OC, n = 8, 22 ± 3 years, weekly strength training: 4.5 ± 1.9 h) were recruited. A one-repetition-maximum (1RM) test and strength exercise in the squat (4 × 10 repetitions, 70%1RM) was performed in the early follicular phase or pill free interval. Concentrations of oestradiol, IL-1β, IL-1ra, IL-6, IL-8, and IL-10 were assessed before (pre), directly after (post) and 24 h after (post24) strength exercise.ResultsIL-1ra increased from pre to post (+ 51.1 ± 59.4%, p = 0.189) and statistically decreased from post to post24 (– 20.5 ± 13.5%, p = 0.011) only in OC. Additionally, IL-1β statistically decreased from post to post24 (– 39.6 ± 23.0%, p = 0.044) only in OC. There was an interaction effect for IL-1β (p = 0.038) and concentrations were statistically decreased at post24 in OC compared to MC (p = 0.05). IL-8 increased across both groups from post to post24 (+ 66.6 ± 96.3%, p = 0.004).ConclusionWe showed a differential regulation of IL-1β and IL-1ra between OC users in the pill-free interval and naturally cycling women 24 h after strength exercise, while there was no effect on other cytokines. Whether this is associated with previously shown compromised morphological adaptations remains to be investigated.

Tear Cytokine Levels in Sicca Syndrome-Related Dry Eye: A Meta-Analysis.

Sjogren's syndrome (SS) is an autoimmune disease that affects exocrine glands, mainly salivary and lacrimal glands. Several studies have investigated cytokine profiles in tears in order to understand the pathogenesis of SS and find additional diagnostic markers. This systematic review and meta-analysis aimed to analyze cytokines in tears of SS patients. A systematic literature search of the Cochrane, Medline via PubMed, Scopus, and Web of Science databases was conducted using key terms related to "Sjögren's syndrome" and "tears" combined with "biomarker", "cytokines", "interleukin", and "chemokines", following PRISMA guidelines. Article selection was subjected to certain eligibility criteria. A total of 17 articles (from 1998 and 2022) were selected for the quantitative and qualitative analysis. When compared to controls, concentrations of IFN-γ, TNF-α, IL-1α, IL-1 Ra, IL-4, IL-6, IL-8, IL-10, IL-17, IL-21 and IL-22 were consistently higher; however, IL-23 was significantly lower in patients with SS compared to the controls. Tear levels of some cytokines were significantly elevated among SS groups compared to control groups. Therefore, these cytokines could be potential biomarkers of SS. However, standardization of sample collection and analytical methods is necessary in order to translate these findings into clinical practice.

Multifocal motor neuropathy is not associated with altered innate immune responses to endotoxin

ObjectiveAntibody- and complement-mediated peripheral nerve inflammation are central in the pathogenesis of MMN. Here, we studied innate immune responses to endotoxin in patients with MMN and controls to further our understanding of MMN risk factors and disease modifiers. MethodsWe stimulated whole blood of 52 patients with MMN and 24 controls with endotoxin and collected plasma. With a multiplex assay, we determined levels of the immunoregulating proteins IL-1RA, IL-1β, IL-6, IL-10, IL-21, TNF-α, IL-8 and CD40L in unstimulated and LPS-stimulated plasma. We compared baseline and stimulated protein levels between patients and controls and correlated concentrations to clinical parameters. ResultsProtein level changes after stimulation were comparable between groups (p > 0.05). IL-1RA, IL-1β, IL-6 and IL-21 baseline concentrations showed a positive correlation with monthly IVIg dosage (all corrected p-values < 0.016). Patients with anti-GM1 IgM antibodies showed a more pronounced IL-21 increase after stimulation (p 0.048). ConclusionsAltered endotoxin-induced innate immune responses are unlikely to be a susceptibility factor for MMN.

The role of genetic polymorphisms of interleukin-1 (IL-1R1 and IL-1RN) in primary knee osteoarthritis in Indonesia

This study aimed to evaluate the association of SNPs of the IL-1 family with the clinical severity of knee OA. This case‒control study was performed among 100 healthy knees and 130 osteoarthritis (OA) knees of people aged ≥ 50 years with a BMI ≥ 25 kg/m2. The possible correlations among clinical findings, radiographic evaluations, serum levels of IL-1R1 and IL-1Ra, and genotype analyses were evaluated. Three SNPs of IL-1R1, rs871659, rs3771202, and rs3917238, were associated with primary knee OA. Females with IL-1R1 SNP rs871659 allele A had a higher prevalence of primary knee OA. No correlation was found between SNPs of IL-1R1 and IL-1RN and clinical or radiologic severity or serum concentrations of IL-1R1 and IL-1Ra (p > 0.05). BMI and IL-1R1 rs3917238 genotype C/C were correlated with moderate-severe VAS scores. A correlation was also found between the EQ-5D-3L self-care dimension and obesity and between the EQ-5D-3L pain and usual activity dimensions and age ≥ 60 and obesity (p < 0.05). Radiologic severity was only associated with age ≥ 60 years (p < 0.05). We found the IL-1R1 SNPs rs871659, rs3771202, and rs3917238 to be predisposing factors for primary knee osteoarthritis. The clinical findings, radiographic severity, and serum concentrations of IL-1R1 and IL-1Ra were not correlated with these gene polymorphisms.