Elevated levels of interleukin‐35 and interleukin‐37 in adult patients with obstructive sleep apnea

BackgroundSystemic inflammation has a critical role in the pathogenesis of obstructive sleep apnea (OSA). Interleukin (IL)‐35 and IL‐37 have been identified as novel immune‐modulating cytokines with anti‐inflammatory activities in numerous types of inflammatory disease. The present study aimed to examine the serum levels of IL‐35 and IL‐37 in patients with OSA, and to investigate their associations with the severity of OSA.MethodsA total of 97 patients, including 67 cases of OSA and 30 age‐ and gender‐matched healthy control subjects, were enrolled in the present study. All subjects were evaluated by overnight polysomnography. Serum IL‐35, IL‐37, and pro‐inflammatory cytokine IL‐1β levels were examined by ELISA.ResultsCompared with those in the control subjects, serum IL‐35, IL‐37, and IL‐1β levels were significantly elevated in patients with mild, moderate, or severe OSA. Furthermore, a severity‐dependent increase in serum IL‐35 and IL‐37 levels was observed in patients with OSA. IL‐35 and IL‐37 levels were positively correlated with the apnea‐hypopnea index (r = 0.742 and 0.578, respectively; both p < 0.001), while they were negatively correlated with the mean oxygen saturation (r = −0.461 and −0.339, respectively; both p < 0.001) and lowest oxyhaemoglobin saturation (r = −0.616 and −0.463, respectively; both p < 0.001) in patients with OSA. In addition, a positive correlation was observed between IL‐35 or IL‐37 and IL‐1β levels (all p < 0.001).ConclusionThe serum levels of IL‐35 and IL‐37 were significantly increased in patients with OSA and associated with the severity of OSA, implying that IL‐35 and IL‐37 may have a protective role in OSA by counteracting inflammatory responses.     

Potential of long non‐coding RNA KCNQ1OT1 as a biomarker reflecting systemic inflammation,multiple organ dysfunction,and mortality risk in sepsis patients

BackgroundLong non‐coding RNA potassium voltage‐gated channel subfamily Q member 1 opposite strand 1 (lnc‐KCNQ1OT1) represses inflammation and multiple organ dysfunction, whereas its clinical value in sepsis is unclear. Thus, this study aimed to explore this issue.MethodsLnc‐KCNQ1OT1 from peripheral blood mononuclear cells were detected by RT‐qPCR in 116 sepsis patients and 60 healthy controls (HCs). Moreover, sepsis patients were followed‐up until death or up to 28 days.ResultsLnc‐KCNQ1OT1 decreased in patients with sepsis than in HCs (p < 0.001). In sepsis patients, lnc‐KCNQ1OT1 was negatively correlated with sequential organ failure assessment (SOFA) scores (r = −0.344, p < 0.001) and several SOFA subscale scores (including respiratory system, coagulation, liver, and renal systems) (all r < 0, p < 0.05). Furthermore, lnc‐KCNQ1OT1 was negatively correlated with CRP (r = −0.386, p < 0.001), TNF‐α (r = −0.332, p < 0.001), IL‐1β (r = −0.319, p < 0.001), and IL‐6 (r = −0.255, p = 0.006). Additionally, lnc‐KCNQ1OT1 levels were lower in sepsis deaths than in sepsis survivors (p < 0.001), and the receiver operating characteristic curve showed that lnc‐KCNQ1OT1 had an acceptable ability to predict 28‐day mortality (area under the curve: 0.780, 95% confidence interval: 0.678–0.882). Meanwhile, its ability to predict 28‐day mortality risk was higher than that of CRP, TNF‐α, IL‐1β, and IL‐6, but slightly lower than the SOFA score and acute physiology and chronic health evaluation II score.ConclusionLnc‐KCNQ1OT1 serves as a potential biomarker for monitoring disease severity and prognosis in patients with sepsis.     

Inter‐alpha‐trypsin inhibitor heavy chain 4: A serologic marker relating to disease risk,activity, and treatment outcomes of rheumatoid arthritis

ObjectiveInter‐alpha‐trypsin inhibitor heavy chain 4 (ITIH4) regulates immunity and inflammation, but its clinical role in rheumatoid arthritis (RA) patients remains unclear. Hence, this study was conducted to explore the association of circulating ITIH4 with disease risk, clinical features, inflammatory cytokines, and treatment outcomes of RA.MethodsAfter the enrollment of 93 active RA patients and 50 health controls (HCs), their serum ITIH4 level was analyzed by enzyme‐linked immunosorbent assay (ELISA). For RA patients only, serum ITIH4 level at week (W) 6 and W12 after treatment was also analyzed. Besides, serum tumor necrosis factor‐alpha (TNF‐α), interleukin (IL)‐1β, IL‐6, and IL‐17A at baseline of RA patients were also detected by ELISA.ResultsITIH4 was downregulated in RA patients (151.1 (interquartile range (IQR): 106.2–213.5) ng/mL) than in HCs (306.8 (IQR: 238.9–435.1) ng/mL) (p < 0.001). Furthermore, ITIH4 was negatively related to C‐reactive protein (CRP) (r_s  = −0.358, p < 0.001) and 28‐joint disease activity score using erythrocyte sedimentation rate (DAS28‐ESR) (r_s  = −0.253, p = 0.014) in RA patients, but not correlated with other clinical features (all p > 0.05). Besides, ITIH4 was negatively linked with TNF‐α (r_s  = −0.337, p = 0.001), IL‐6 (r_s  = −0.221, p = 0.033), and IL‐17A (r_s  = −0.368, p < 0.001) in RA patients, but not correlated with IL‐1β (r_s  = −0.195, p = 0.061). Moreover, ITIH4 was gradually elevated in RA patients from baseline to W12 after treatment (p < 0.001). Additionally, the increment of ITIH4 at W6 and W12 was linked with treatment response and remission in RA patients (all p < 0.05).ConclusionCirculating ITIH4 possesses clinical utility in monitoring disease risk, inflammation, disease activity, and treatment outcomes of RA.     

The relation of common inflammatory cytokines with anxiety and depression and their values in estimating cardiovascular outcomes in coronary heart disease patients

BackgroundInflammatory cytokines are associated with the occurrence and severity of psychological disorders in cerebro‐cardiovascular disease patients. This study aimed to investigate the correlation of inflammatory cytokines with anxiety and depression in coronary heart disease (CHD) patients and their values for estimating cardiovascular outcomes.MethodsTotally, 150 CHD patients and 50 healthy subjects were enrolled. Then, tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐6, IL‐10, and IL‐17 in their serum samples were detected using ELISA assay; anxiety and depression were assessed by the HADS score. For CHD patients, major adverse cardiac events (MACE) were recorded and evaluated.ResultsCHD patients presented with increased TNF‐α (median: 50.0 vs. 37.0 pg/ml, p < 0.001), IL‐1β (median: 2.7 vs. 2.0 pg/ml, p < 0.001), IL‐6 (median: 24.7 vs. 24.3 pg/ml, p = 0.032), IL‐17A (median: 58.6 vs. 43.6 pg/ml, p < 0.001), HADS‐A score (p < 0.001), HADS‐D score (p < 0.001), anxiety rate (p < 0.001), and depression rate (p < 0.001) compared to healthy subjects. Then, TNF‐α (p = 0.003), IL‐1β (p = 0.023), and IL‐17A (p < 0.001) were related to elevated HADS‐A score. Also, TNF‐α (p = 0.014) and IL‐17A (p = 0.020) positively, while IL‐10 (p = 0.047) negatively related to the HADS‐D score in CHD patients. Interestingly, elevated TNF‐α and IL‐17A were associated with anxiety and depression occurrence in CHD patients (all p < 0.05). Inspiringly, only TNF‐α high, but not other cytokines, was related to elevated accumulating MACE (p = 0.041), while no correlation of anxiety (p = 0.173) or depression (p = 0.068) with accumulating MACE was observed.ConclusionTNF‐α and IL‐17A correlate with anxiety and depression, while only TNF‐α high is related to elevated accumulating MACE in CHD patients.     

Clinical value of serum JKAP in acute ischemic stroke patients

BackgroundJun N‐terminal kinase pathway‐associated phosphatase (JKAP) regulates neuronal function, T helper (Th) 1/2/17 cell differentiation, and inflammatory process, but its clinical role in acute ischemic stroke (AIS) patients remains unclear. Hence, this study intended to evaluate JKAP level and its relationship with disease severity, Th1, 2, 17 secreted cytokines, adhesion molecules, and prognosis of AIS patients.MethodsSerum JKAP of 122 AIS patients and 50 controls was detected by ELISA. For AIS patients only, Th1, 2, 17 secreted cytokines IFN‐γ, IL‐4, IL‐17; TNF‐α, ICAM‐1, and VCAM‐1 were also detected by ELISA.ResultsJKAP was decreased in AIS patients compared with controls (46.350 (interquartile range (IQR): 34.250–59.875) pg/ml vs. 84.500 (IQR: 63.175–113.275) pg/ml, p < 0.001), which could distinguish AIS patients from controls (area under curve (AUC): 0.810, 95% confidence interval (CI): 0.732–0.888). In AIS patients, JKAP negatively linked with the National Institutes of Health Stroke Scale (NIHSS) score (r_s  = −0.342, p < 0.001); besides, it was positively related to IL‐4 (r_s  = 0.213, p = 0.018) and negatively associated with IL‐17 (r_s  = −0.270, p = 0.003) but not related to IFN‐γ (r_s  = −0.146, p = 0.109). Furthermore, elevated JKAP associated with declined TNF‐α (r_s  = −0.219, p = 0.015) and ICAM‐1 (r_s  = −0.235, p = 0.009) but not related to VCAM‐1 (r_s  = −0.156, p = 0.085). Besides, declined JKAP was linked with 2‐year recurrence (p = 0.027) and 3‐year recurrence (p = 0.010) in AIS patients; while JKAP was not related to 1‐year recurrence or death risk (both p > 0.050).ConclusionJKAP may sever as a candidate prognostic biomarker in AIS patients, indicating its potency for AIS management.     

Low serum interleukin‐38 levels in patients with Graves’ disease and Hashimoto’s thyroiditis

BackgroundAutoimmune thyroid disease (AITD) mainly includes Graves’ disease (GD) and Hashimoto''s thyroiditis (HT), which is caused by individual genetics, autoimmune dysfunction, and a variety of external environmental factors. Interleukin (IL)‐38 is involved in a wide range of autoimmune diseases, but little is known about IL‐38 expression in AITD.MethodsFifty patients with GD, 50 with HT, and 50 healthy controls (HC) were enrolled in this study. Basic information of the participants was obtained through a physical examination. Immunological data were obtained by an automatic chemiluminescence immunoanalyzer. C‐reactive protein (CRP) concentrations and the white blood cell count were measured. Serum IL‐38 levels were determined by an enzyme‐linked immunosorbent assay.ResultsSerum IL‐38 levels were significantly lower in the GD and HT groups than in the HC group (both p < 0.01). Serum CRP concentrations were significantly lower in the HT group than in the HC group (p < 0.05). Receiver operating characteristic curve analysis showed that the area under the curve was 0.7736 (p < 0.01) for IL‐38 and 0.7972 (p < 0.01) for IL‐38 combined with CRP in the GD group. In the HT group, the area under the curve was 0.7276 (p < 0.01) for IL‐38 and 0.7300 for IL‐38 combined with CRP (p < 0.01).ConclusionsThe results suggest that serum IL‐38 level is a potential new diagnostic biomarker in patients with GD and HT.     

Comparison of IL‐6 measurement methods with a special emphasis on COVID‐19 patients according to equipment and sample type

BackgroundInterleukin‐6 (IL‐6) is a multifunctional cytokine associated with various diseases, including coronavirus disease (COVID‐19). Although IL‐6 levels can be assessed using serum samples, use of the AFIAS (Boditech Med Inc.) automated immunoassay analyzer enables quick and simple measurement of IL‐6 levels in both serum and whole blood specimens. This study aimed to assess the correlation between IL‐6 measurements obtained from the AFIAS IL‐6 assay and Elecsys IL‐6 assay (Roche Diagnostics). Additionally, utilization of the AFIAS IL‐6 assay was evaluated.MethodsThe IL‐6 levels from 113 serum samples quantified using two assay systems were evaluated for their degree of correlation. Meanwhile, the linearity, analytical sensitivity, and precision/reproducibility of the AFIAS IL‐6 assay were also assessed.ResultsQuantification of IL‐6 with the AFIAS IL‐6 and Elecsys IL‐6 assays showed excellent agreement (kappa 0.802) and were found to be correlated (y = −0.2781 + 1.068x; 95% confidence interval: 1.007–1.124). AFIAS IL‐6 showed good analytical performances. IL‐6 levels were significantly higher in deceased patients compared to those with non‐complicated disease and those who were intubated (p = 0.002 and p < 0.0001, respectively). Finally, IL‐6 levels more accurately predicted poor prognosis in patients, than did C‐reactive protein (area under the curve, 0.716 vs. 0.634).ConclusionThe overall analytical performance of the AFIAS assay was comparable to that of the Elecsys IL‐6 assay. In light of the ongoing COVID‐19 pandemic, the AFIAS may be an attractive tool for measuring IL‐6 levels.     

Colchicine,COVID‐19 and hematological parameters: A meta‐analysis

IntroductionColchicine has the potential in reducing patient morbidity and mortality in COVID‐19 infection owing to its anti‐inflammatory properties. This study aims to determine the efficacy of colchicine in optimizing inflammatory hematological biomarker levels among COVID‐19 patients.MethodsIn accordance to Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) 2020 statement guidelines, a systematic search was conducted using the following keywords: Colchicine, covid*, SARS‐CoV‐2, anti‐inflammatory, trials, clinical, hematological, laboratory. Databases were searched from December 2019 until August 26, 2021: MEDLINE/PubMed, Web of Science, Cochrane, Scopus, and EMBASE. Other sources were located through ClinicalTrials.Gov, manually searching SAGE, Science Direct, Elsevier, and Google Scholar. The meta‐analysis was conducted using Review Manager 5.4.ResultsIn total, six studies were included, of which four reported c‐reactive protein (CRP) standardized mean reductions in the colchicine group (N = 165) as opposed to the control (N = 252; SMD = −0.49, p < 0.001). On noting lactate dehydrogenase (LDH) values post treatment, the colchicine group (N = 204) showed significant reductions at the end of treatment compared to control (N = 290; SMD = −0.85, p < 0.001). Finally, the D‐dimer values in colchicine groups (N = 129) compared to control (N = 216) also documented a negative effect size (SMD = −0.9, p < 0.001).ConclusionColchicine has efficacy in reducing inflammatory biomarkers observed in moderate‐to‐severe COVID‐19 patients. It may be worthwhile to consider monitoring the clinical and laboratory parameters of patients in further trials to consider colchicine as a strong candidate for an adjunct to COVID‐19 treatment.     

Combined detection of procalcitonin,heparin‐binding protein,and interleukin‐6 is a promising assay to diagnose and predict acute pancreatitis

BackgroundAcute pancreatitis (AP), one of the most common clinical emergencies, is characterized by variable clinical features and inadequate diagnostic methods. At present, the commonly used indicators do not have high specificity and do not necessarily reflect disease severity. We therefore aimed to investigate diagnostic and prognostic value of plasma procalcitonin, heparin‐binding protein, and interleukin‐6 for acute pancreatitis by separate detection and joint detection.MethodsThe study involved 451 participants, including 343 AP patients and 108 healthy controls. We analyzed the association of the three biomarkers with the severity and prognosis of AP.ResultsA statistically significant increase in the mean plasma analyte levels was detected in the study group compared to the control group. Multivariate comparison showed that plasma levels of PCT, HBP, and IL‐6 were all significantly different among the three groups at different sampling times (1st, 3rd, 7th, and 10th day of admission) (p < 0.01). The combination of the three indicators had significantly higher diagnostic value than either the individual markers or pairwise combinations (p < 0.001). The levels of the three were all significantly higher in severe acute pancreatitis (SAP) patients than in non‐SAP patients (p < 0.001); meanwhile, patients with high levels had a worse prognosis than those with low levels (p < 0.05). In multivariate analysis adjusted for age and sex, high levels of PCT, HBP, and IL‐6 were found to be independently associated with the development of AP.ConclusionsIt dramatically improved the diagnostic power of AP when PCT, HBP, and IL‐6 were combined; high PCT, HBP, and IL‐6 levels within 3 days of admission may be the potentially useful indicators for predicting SAP.     

Topical inflammasome inhibition with disulfiram prevents irritant contact dermatitis

BackgroundThe pathogenesis of contact dermatitis, a common inflammatory skin disease with limited treatment options, is held to be driven by inflammasome activation induced by allergens and irritants. We here aim to identify inflammasome‐targeting treatment strategies for irritant contact dermatitis.MethodsA high content screen with 41,184 small molecules was performed using fluorescent Apoptosis associated speck‐like protein containing a CARD (ASC) speck formation as a readout for inflammasome activation. Hit compounds were validated for inhibition of interleukin (IL)‐1β secretion. Of these, the approved thiuramdisulfide derivative disulfiram was selected and tested in a patch test model of irritant contact dermatitis in 25 healthy volunteers. Topical application of disulfiram, mometasone or vehicle was followed by application of sodiumdodecylsulfate (SDS) for 24 h each. Eczema induction was quantified by mexameter and laser speckle imaging. Corneocyte sampling of lesional skin was performed to assess inflammasome‐mediated cytokines IL‐1β and IL‐18.ResultsDisulfiram induced a dose‐dependent inhibition of ASC speck formation and IL‐1β release in cellular assays in vitro. In vivo, treatment with disulfiram, but not with vehicle and less mometasone, inhibited SDS‐induced eczema. This was demonstrated by significantly lower erythema and total perfusion values assessed by mexameter and laser speckle imaging for disulfiram compared to vehicle (p < 0.001) and/or mometasone (p < 0.001). Also, corneocyte IL‐18 levels were significantly reduced after application of disulfiram compared to vehicle (p < 0.001).ConclusionWe show that disulfiram is a dose‐dependent inhibitor of inflammasome pathway activation in vitro and inhibitor of SDS‐induced eczema in vivo. Topical application of disulfiram represents a potential treatment option for irritant contact dermatitis.     

Effects of IL‐32 polymorphisms and IL‐32 levels on the susceptibility and severity of coronary artery disease

BackgroundInterleukin‐32 (IL‐32) has long been proposed as a biomarker for coronary artery disease (CAD). We aimed to evaluate the association between IL‐32 levels and coronary stenosis severity, IL‐32 polymorphisms rs28372698 and rs4786370, and CAD susceptibility.MethodsA total of 362 patients with definite or suspected CAD that underwent angiography were recruited (CAD group, n = 175; nonobstructive CAD group, n = 56; control group, n = 131). The severity of coronary stenosis was assessed using the Gensini score and the number of diseased vessels. IL‐32 levels were determined using enzyme‐linked immunosorbent assay. Gene polymorphisms were genotyped using PCR and sequencing techniques.ResultsIL‐32 levels were significantly different at different levels of coronary artery stenosis (p < 0.05), and logIL‐32 was positively correlated with the Gensini score (r = 0.357, p < 0.01). Multivariate logistic regression analysis revealed that IL‐32 was independently associated with CAD (OR = 6.526, 95% CI: 3.344–12.739, p < 0.01). The receiver operating characteristic analysis revealed the area under the curve for discriminating the CAD and Gensini score were 0.605 and 0.613, respectively. Furthermore, IL‐32 levels were significantly higher before percutaneous coronary intervention (PCI) than at 7 days post‐PCI (p = 0.012). The homozygous TT genotype and T allele of rs28372698 were found to be associated with increased risk of CAD, while TT homozygosity and the T allele of rs4786370 with reduced risk of CAD (p < 0.05). However, both SNPs had no obvious effect on IL‐32 levels or coronary stenosis severity in patients with CAD.ConclusionTo the best of our knowledge, our study is the first to show that rs28372698 and rs4786370 are associated with CAD susceptibility in Chinese Han population. We also suggest that plasma IL‐32 levels may be indicative of coronary artery stenosis and the efficacy of PCI and provide guidance for risk stratification and disease management.     

Low levels of serum IL‐39 are associated with autoimmune thyroid disease

BackgroundInterleukin (IL)‐39 is a novel member of IL‐12 cytokine family, but its role in autoimmune thyroid diseases (AITD) is unclear. The aim of the present study was to determine serum levels of IL‐39 in Hashimoto''s thyroiditis (HT) and Graves'' disease (GD) patients.MethodsA total of 48 patients with HT, 50 patients with GD, and 45 healthy controls (HCs) were recruited for this study. Levels of serum IL‐39 were determined by ELISA.ResultsCompared with HC group, levels of serum IL‐39 in patients with HT (p < 0.05) and GD (p < 0.01) were drastically reduced. Among patients with HT, serum IL‐39 levels had a positive correlation with white blood cell count (WBC) count and free triiodothyronine level. Among patients with GD, the levels of IL‐39 in serum were positively correlated with WBC count and C‐reactive protein levels.ConclusionsIL‐39 may be a new potential predictor for patients with HT and GD.     

Effects of anti‐IL5 biological treatments on blood IgE levels in severe asthmatic patients: A real‐life multicentre study (BIONIGE)

BackgroundMepolizumab and benralizumab are clinically effective biological treatments for severe eosinophilic asthmatic patients by hampering eosinophilic inflammation. The effects of these compound on the immunoglobulin (Ig)E T2 component are virtually unknown.ObjectivesTo evaluate the change in total IgE levels at 4 ± 2 months after initiation of the mepolizumab (primary outcome) or benralizumab. When available, the changes of blood inflammatory cell counts, lung function and asthma control test (ACT) were also assessed and correlated with changes in total IgE levels.MethodsObservational, retrospective, multicentre, cohort study. Severe eosinophilic atopic asthmatic patients treated with mepolizumab or benralizumab were included in the analysis.ResultsThree‐month treatment (on average) with mepolizumab (n = 104) or benralizumab (n = 82) resulted in significantly higher reduction of blood eosinophil and basophil levels in patients treated with benralizumab compared to mepolizumab. Mepolizumab did not significantly modified the levels of blood total IgE during the study period, whereas benralizumab significantly reduced (−35%, p < 0.001) total blood IgE levels. In patients treated with benralizumab the reduction of blood total Ig‐E levels correlated with the reduction of blood basophils (but not eosinophils) and weakly with the improvement of asthma control.ConclusionBenralizumab but not mepolizumab, treatment led to a significant reduction of circulating IgE level. The study provides different and specific mechanisms of action for anti‐IL5‐pathway treatments.     

Longitudinal variation of circulating Inc‐ITSN1‐2: A novel biomarker reflecting disease severity,inflammation, recurrence,and death risk in acute ischemic stroke patients

BackgroundLong noncoding RNA intersectin 1–2 (lnc‐ITSN1‐2) regulates inflammation and neuronal apoptosis; meanwhile, the latter two factors participate in the pathogenesis of acute ischemic stroke (AIS). Therefore, this study detected lnc‐ITSN1‐2 at multiple time points, aiming to explore its longitudinal variation and clinical value in the management of AIS patients.MethodsThe current study enrolled 102 AIS patients, then detected their lnc‐ITSN1‐2 in peripheral blood mononuclear cell (PBMC) at baseline (D0), day (D)1, D3, D7, month (M)1, M3, M6, and year (Y)1 after admission using RT‐qPCR. Additionally, lnc‐ITSN1‐2 in PBMC of 50 controls was also detected.ResultsLnc‐ITSN1‐2 was up‐regulated in AIS patients than that in controls (p < 0.001). Lnc‐ITSN1‐2 positively associated with NIHSS score, TNF‐α, and IL‐17A (all p < 0.050) but was not linked with IL‐6 (p = 0.093) in AIS patients. Notably, lnc‐ITSN1‐2 was gradually increased from D0 to D3; while it switched to decrease from D3 to Y1 in AIS patients. Lnc‐ITSN1‐2 disclosed similar longitudinal variation during 1 year in non‐recurrent (p < 0.001), recurrent (p = 0.001), and survived patients (p < 0.001), while the variation of lnc‐ITSN1‐2 in died patients was not obvious (p = 0.132). More importantly, lnc‐ITSN1‐2 at D0, D3, D7, M1, M3, M6, and Y1 was higher in recurrent AIS patients than that in non‐recurrent AIS patients (all p < 0.050); moreover, lnc‐ITSN1‐2 at D3, D7, M1, M3, and M6 was up‐regulated in died AIS patients than AIS survivors (all p < 0.050).ConclusionThe dynamic variation of Inc‐ITSN1‐2 could serve as a biomarker reflecting disease severity, inflammatory cytokines, recurrence, and death risk in AIS patients.