Molecular Characterization, 3D Modeling of Grass Carp Interleukin-10 Receptor 1 (IL10R1)

Interleukin-10 (IL-10) is an important cytokine that plays a pivotal role in natural and adaptive immune systems. However, in lower vertebrates, especially in teleost the receptor of this cytokine is still largely unknown. This paper described the cloning and characterization of grass carp interleukin-10 receptor 1 (gcIL10R1) and the 3D structure of its extracellular domain was predicted. The gcIL10R1 cDNA included 180 bp5’ untranslated region (UTR), 870 bp3’ UTR and an open reading frame (ORF) of 1632 bp. The ORF was found to encode a 543 amino acid protein with a putative JAK1 binding site, one STAT3 binding site. The phylogenetic analysis clusters gcIL10R1 with other teleost IL10R1s but independently of the amphibian, avian and mammalian IL10R1s. The 3D structure of its extracellular domain was the first homology model of a fish IL10R1 that revealed a high similarity with its mammalian and avian counterparts.

Exploring the role of interleukin-6 receptor blockade in epilepsy and associated neuropsychiatric conditions through a mendelian randomization study

BACKGROUND The interplay between inflammation,immune dysregulation,and the onset of neurological disorders,including epilepsy,has become increasingly recognized.Interleukin(IL)-6,a pro-inflammatory cytokine,is suspected to not only mediate traditional inflammatory pathways but also contribute to neuroinflammatory responses that could underpin neuropsychiatric symptoms and broader psychiatric disorders in epilepsy patients.The role of IL-6 receptor(IL6R)blockade presents an intriguing target for therapeutic intervention due to its potential to attenuate these processes.neuropsychiatric conditions due to neuroinflammation.METHODS Mendelian randomization(MR)analysis employing single nucleotide poly-morphisms(SNPs)in the vicinity of the IL6R gene(total individuals=408225)was used to evaluate the putative causal relationship between IL6R blockade and epilepsy(total cases/controls=12891/312803),focal epilepsy(cases/controls=7526/399290),and generalized epilepsy(cases/controls=1413/399287).SNP weights were determined by their effect on C-reactive protein(CRP)levels and integrated using inverse variance-weighted meta-analysis as surrogates for IL6R effects.To address potential outlier and pleiotropic influences,sensitivity analyses were conducted employing a variety of MR methods under different modeling assumptions.RESULTS The genetic simulation targeting IL6R blockade revealed a modest but significant reduction in overall epilepsy risk[inverse variance weighting:Odds ratio(OR):0.827;95%confidence interval(CI):0.685-1.000;P=0.05].Subtype analysis showed variability,with no significant effect observed in generalized,focal,or specific childhood and juvenile epilepsy forms.Beyond the primary inflammatory marker CRP,the findings also suggested potential non-inflammatory pathways mediated by IL-6 signaling contributing to the neurobiological landscape of epilepsy,hinting at possible links to neuroinflammation,psychiatric symptoms,and associated mental disorders.CONCLUSION The investigation underscored a tentative causal relationship between IL6R blockade and decreased epilepsy incidence,likely mediated via complex neuroinflammatory pathways.These results encouraged further in-depth studies involving larger cohorts and multifaceted psychiatric assessments to corroborate these findings and more thoroughly delineate the neuro-psychiatric implications of IL-6 signaling in epilepsy.The exploration of IL6R blockade could herald a novel therapeutic avenue not just for seizure management but also for addressing the broader psychiatric and cognitive disturbances often associated with epilepsy.

Synergistic effect of interleukin-10-receptor variants in a case of early-onset ulcerative colitis

AIM: To investigated the molecular cause of very early-onset ulcerative colitis (UC) in an 18-mo-old affected child.

Low interleukin-10 level indicates a good prognosis in Salmonella enterica serovar typhimurium-induced pediatric hemophagocytic lymphohistiocytosis:A case report

BACKGROUND Secondary hemophagocytic lymphohistiocytosis(sHLH)triggered by Salmonella enterica serovar Typhimurium is rare in pediatric patients.There is no consensus on how to treat S.typhimurium-triggered sHLH.CASE SUMMARY A 9-year-old boy with intermittent fever for 3 d presented to our hospital with positive results for S.typhimurium,human rhinovirus,and Mycoplasma pneumoniae infections.At the time of admission to our institution,the patient’s T helper 1/T helper 2 cytokine levels were 326 pg/mL for interleukin 6(IL-6),9.1 pg/mL for IL-10,and 246.7 pg/mL for interferon-gamma(IFN-γ),for which the ratio of IL-10 to IFN-γwas 0.04.In this study,the patient received meropenem,linezolid,and cefoperazone/sulbactam in combination with high-dose methylprednisolone therapy(10 mg/kg/d for 3 d)and antishock supportive treatment twice.After careful evaluation,this patient did not receive HLH chemotherapy and recovered well.CONCLUSION S.Typhimurium infection-triggered sHLH patient had a ratio of IL-10 to IFN-γ≤1.33,an IL-10 concentration≤10.0 pg/mL,and/or an IFN-γconcentration≤225 pg/mL at admission.Early antimicrobial and supportive treatment was sufficient,and the HLH-94/2004 protocol was not necessary under these conditions.

Effects of interleukin-10 treated macrophages on bone marrow mesenchymal stem cells via signal transducer and activator of transcription 3 pathway

BACKGROUND Alveolar bone defects caused by inflammation are an urgent issue in oral implant surgery that must be solved.Regulating the various phenotypes of macrophages to enhance the inflammatory environment can significantly affect the progression of diseases and tissue engineering repair process.AIM To assess the influence of interleukin-10(IL-10)on the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)following their interaction with macrophages in an inflammatory environment.METHODS IL-10 modulates the differentiation of peritoneal macrophages in Wistar rats in an inflammatory environment.In this study,we investigated its impact on the proliferation,migration,and osteogenesis of BMSCs.The expression levels of signal transducer and activator of transcription 3(STAT3)and its activated form,phos-phorylated-STAT3,were examined in IL-10-stimulated macrophages.Subsequently,a specific STAT3 signaling inhibitor was used to impede STAT3 signal activation to further investigate the role of STAT3 signaling.RESULTS IL-10-stimulated macrophages underwent polarization to the M2 type through substitution,and these M2 macrophages actively facilitated the osteogenic differentiation of BMSCs.Mechanistically,STAT3 signaling plays a crucial role in the process by which IL-10 influences macrophages.Specifically,IL-10 stimulated the activation of the STAT3 signaling pathway and reduced the macrophage inflammatory response,as evidenced by its diminished impact on the osteogenic differentiation of BMSCs.CONCLUSION Stimulating macrophages with IL-10 proved effective in improving the inflammatory environment and promoting the osteogenic differentiation of BMSCs.The IL-10/STAT3 signaling pathway has emerged as a key regulator in the macrophage-mediated control of BMSCs’osteogenic differentiation.

Interleukin-6 in epilepsy and its neuropsychiatric comorbidities: How to bridge the gap

There is growing evidence that interleukin(IL)-6 plays an important role in neurological and psychiatric disorders.This editorial comments on the study published in the recent issue of the World Journal of Psychiatry,which employed Mendelian randomization to identify a causal relationship between IL-6 receptor blockade and decreased epilepsy incidence.The purpose of this editorial is to highlight the dual effects of IL-6 in epilepsy and its related neuropsychiatric comorbidities.IL-6 plays a critical role in the facilitation of epileptogenesis and maintenance of epileptic seizures and is implicated in neuroinflammatory proce-sses associated with epilepsy.Furthermore,IL-6 significantly influences mood regulation and cognitive dysfunction in patients with epilepsy,highlighting its involvement in neuropsychiatric comorbidities.In summary,IL-6 is not only a pivotal factor in the pathogenesis of epilepsy but also significantly contributes to the emergence of epilepsy-related neuropsychiatric complications.Future resear-ch should prioritize elucidating the specific mechanisms by which IL-6 operates across different subtypes,stages and neuropsychiatric comorbidities of epilepsy,with the aim of developing more precise and effective interventions.Furthermore,the potential of IL-6 as a biomarker for the early diagnosis and prognosis of epile-psy warrants further investigation.

Interleukin-17A facilitates tumor progression via upregulating programmed death ligand-1 expression in hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in the tumor microenvir-onment.Inflammation regulates the expression of programmed death ligand-1(PD-L1)in the immunosuppressive tumor microenvironment and affects im-munotherapy efficacy.Interleukin-17A(IL-17A)is involved in the remodeling of the tumor microenvironment and plays a protumor or antitumor role in different tumors.We hypothesized that IL-17A participates in tumor progression by affe-cting the level of immune checkpoint molecules in HCC.The upregulation of PD-L1 expression in HCC cells by IL-17A was assessed by reverse transcription PCR,western blotting,and flow cytometry.Mechanistic studies were conducted with gene knockout models and pathway inhibitors.The function of IL-17A in immune evasion was explored through coculture of T cells and HCC cells.The effects of IL-17A on the malignant biological behaviors of HCC cells were evaluated in vitro,and the antitumor effects of an IL-17A inhibitor and its synergistic effects with a PD-L1 inhibitor were studied in vivo.RESULTS IL-17A upregulated PD-L1 expression in HCC cells in a dose-dependent manner,whereas IL-17A receptor knockout or treatment with a small mothers against decapentaplegic 2 inhibitor diminished the PD-L1 expression induced by IL-17A.IL-17A enhanced the survival of HCC cells in the coculture system.IL-17A increased the viability,G2/M ratio,and migration of HCC cells and decreased the apoptotic index.Cyclin D1,VEGF,MMP9,and Bcl-1 expression increased after IL-17A treatment,whereas BAX expression decreased.The combination of IL-17A and PD-L1 inhibitors showed synergistic antitumor efficacy and increased cluster of differentiation 8+T lymphocyte infiltration in an HCC mouse model.CONCLUSION IL-17A upregulates PD-L1 expression via the IL-17A receptor/phosphorylation-small mothers against decapenta-plegic 2 signaling pathway in HCC cells.Blocking IL-17A enhances the therapeutic efficacy of PD-L1 antibodies in HCC in vivo.

C-X-C chemokine receptor type 5+CD8+T cells as immune regulators in hepatitis Be antigen-positive chronic hepatitis B under interferonalpha treatment

BACKGROUND C-X-C chemokine receptor type 5(CXCR5)+CD8+T cells represent a unique immune subset with dual roles,functioning as cytotoxic cells in persistent viral infections while promoting B cell responses.Despite their importance,the specific role of CXCR5+CD8+T cells in chronic hepatitis B(CHB),particularly during interferon-alpha(IFN-α)treatment,is not fully understood.This study aims to elucidate the relationship between CXCR5+CD8+T cells and sustained serologic response(SR)in patients undergoing 48 weeks of pegylated IFN-α(peg-IFN-α)treatment for CHB.AIM To elucidate the relationship between CXCR5+CD8+T cells and sustained SR in patients undergoing 48 weeks of peg-IFN-αtreatment for CHB.METHODS This study enrolled 60 patients with hepatitis Be antigen(HBeAg)-positive CHB undergoing 48 weeks of peg-IFN-αtreatment.Participants were assessed for eligibility based on criteria such as persistent HBsAg-positive status for at least six months,HBeAb-negative,hepatitis B virus DNA levels exceeding 2×104 copies/mL,and alanine aminotransferase(ALT)levels between 2 and 10 times the upper limit of normal.Blood samples were collected at baseline and at weeks 12,24,48,and a 24-week treatment-free follow-up(week 72)to measure serum interleukin(IL)-21 concentration via ELISA and to analyze CXCR5 and programmed death-ligand 1(PD-L1)expression on CD8+T cells by flow cytometry,CXCR5 is a chemokine receptor that directs immune cells to specific tissues,while PD-L1 is a protein that regulates immune responses by inhibiting T cell activity.RESULTS Patients with CHB exhibited significantly lower levels of circulating CXCR5+CD8+T cells compared to healthy controls(P<0.01).Notably,CXCR5+CD8+T cells were prominently expressed in patients who achieved sustained SR compared to non-SR(NSR).A significant correlation was observed between CXCR5 and PD-L1 expression(r=-0.189,P=0.002).However,there was no significant correlation between serum IL-21 levels and CXCR5+CD8+lymphocytes(r=-0.03,P=0.625)or serum ALT levels(r=0.026,P=0.678).CONCLUSION The enhanced expression of CXCR5+CD8+T cells in patients achieving HBeAg seroconversion during IFN-αtreatment suggests that these cells play a crucial role in antiviral immune responses against hepatitis B.This study highlights the potential of CXCR5+CD8+T cells as immune regulators in CHB,which may inform future therapeutic strategies to optimize antiviral treatments.

Serum Levels of Interleukin-2 and -10 in Patients with Early Syphilis

Objective: To investigate the roles of interleukin-2(IL-2) and interleukin-10 (IL-10) in pathogenesis ofearly syphilis. Methods: The serum levels of IL-2 and IL-10 in 48patients with early syphilis were detected by ABC-ELISA. Results: (1) The level of IL-2 in the patients withearly syphilis was significantly higher than that inhealthy controls, while that of IL-10 was lower(P<0.001 and P<0.001). (2) The levels of IL-2 and IL-10 were almost identical in patients with primary andsecondary syphilis (P>0.05), as well as between dif-ferent RPR titers (P>0.05). (3) After therapy, the levelof IL-2 decreased markedly (P<0.05), while that of IL-10 increase (p>0.05). (4) A significant correlation wasfound between the serum levels of IL-2 and IL-10 (r=0.5385 P<0.05). Conclusions: Th1 up-regulation occurs in patientswith early syphilis, and plays an active role in fightingagainst TP infection.

外周血CXCL10及其受体CXCR3在复发性生殖器疱疹病毒2型感染患者中表达及其与预后关系研究

目的探讨外周血CXC趋化因子配体10(CXCL10)及其CXC趋化因子受体3(CXCR3)在复发性生殖器疱疹病毒2型感染患者中的表达及其与预后的关系。方法选取2019年7月—2020年7月医院收治的102例复发性生殖器疱疹病毒2型感染患者,另选取同期来院体检的94例健康者,比较复发性生殖器疱疹病毒2型感染患者与健康体检者外周血CXCL10和CXCR3水平。根据临床分期,将102例复发性生殖器疱疹病毒2型感染患者分为发作期(44例)和稳定期(58例),比较发作期和稳定期患者外周血CXCL10和CXCR3水平。随访1年,统计患者复发情况,采用单因素分析影响复发性生殖器疱疹病毒2型感染患者频繁复发的因素,并对其因素进行Logistic回归分析,采用受试者工作特征曲线(ROC)分析外周血CXCL10和CXCR3水平预测复发性生殖器疱疹病毒2型感染患者频繁复发的价值。结果复发性生殖器疱疹病毒2型感染患者外周血CXCL10和CXCR3水平低于健康体检者(P<0.05);发作期患者外周血CXCL10和CXCR3水平低于稳定期患者(P<0.05);随访1年,102例复发性生殖器疱疹病毒2型感染患者中共有28例频繁复发,频繁复发患者性伙伴个数3个及以上构成比高于非频繁复发患者(P<0.05),频繁复发患者外周血干扰素-γ(IFN-γ)、CXCL10和CXCR3水平均低于非频繁复发患者(P<0.05);Logistic多因素回归分析显示性伙伴个数、CXCR3和CXCL10均是影响复发性生殖器疱疹病毒2型感染患者频繁复发的独立危险因素(P<0.05);ROC分析显示,外周血CXCL10和CXCR3预测复发性生殖器疱疹病毒2型感染患者频繁复发的最佳截断点分别为10.14 pg/mL和8.20 ng/mL,曲线下面积(AUC)分别为0.806和0.822,二者联合的特异度和AUC分别为91.89%和0.914。结论复发性生殖器疱疹病毒2型感染患者CXCL10和CXCR3水平均异常降低,二者均与患者频繁复发密切相关,可作为临床预测复发性生殖器疱疹病毒2型感染患者频繁复发的敏感指标。

原发性肝癌组织CCR7、MCM10蛋白与临床病理特征及预后的相关性

目的 探讨原发性肝癌(PHC)组织趋化因子受体7(CCR7)、微染色体维持蛋白10(MCM10)与临床病理特征及预后的相关性。方法 选取2017年1月至2020年12月周口市中心医院90例PHC患者为研究对象,均行肝癌切除术,术中取肿瘤组织及癌旁正常组织。比较PHC不同组织CCR7、MCM10蛋白表达,χ^(2)检验分析CCR7、MCM10表达与临床病理特征的关系,Kaplan-Meier分析CCR7、MCM10蛋白表达与PHC患者预后的关系,Cox回归分析PHC患者预后影响因素,Kaplan-Meier分析CCR7、MCM10蛋白表达亚组与PHC患者预后的关系。结果 PHC患者肿瘤组织中CCR7、MCM10蛋白阳性表达分别为66.67%、75.56%,高于正常组织的23.33%、27.78%,差异有统计学意义(P<0.05);有淋巴结转移、血管侵犯患者癌组织中CCR7、MCM10蛋白阳性表达率(79.25%、94.34%,81.58%、89.47%)高于无淋巴结转移、血管侵犯患者(48.65%、48.65%,55.77%、65.38%),差异有统计学意义(P<0.05);Kaplan-Meier生存分析显示,CCR7、MCM10蛋白阳性表达患者的3 a生存率分别为39.66%(23/58)、41.54%(27/65),低于阴性表达患者的68.97%(20/29)、72.73%(16/22),差异有统计学意义(P<0.05);Cox回归分析显示,淋巴结转移(95%CI:1.129~3.025)、血管侵犯(95%CI:1.463~3.147)、CCR7蛋白(95%CI:1.407~3.524)、MCM10蛋白(95%CI:1.384~3.441)均为PHC患者预后的独立危险因素(P<0.05);Kaplan-Meier分析显示,CCR7蛋白阳性+MCM10蛋白阳性亚组预后最差,CCR7蛋白阴性+MCM10蛋白阴性亚组预后最好,各亚组间比较差异均有统计学意义(P<0.05)。结论 PHC组织CCR7、MCM10蛋白表达与临床病理特征及预后相关,二者均阳性表达是预后不良的危险因素,可作为临床评估病情、预测预后的辅助指标,并对临床防治具有一定指导意义。

Why interleukin-10 supplementation does not work in Crohn's disease patients

Inflammatory bowel diseases (IBD) such as Crohn's disease (CD) or ulcerative colitis are chronic intestina disorders, which are on the increase in "Westernised" countries. IBD can be caused by both genetic and environmental factors. Interleukin-10 (IL-10) is an immunoregulatory cytokine that has been identified as being involved in several diseases including IBD. Studies have shown that polymorphisms in the promoter region reduce serum levels of IL-10 and this reduction has been associated with some forms of IBD. Mouse models have shown promising results with IL-10 supplementation, as such IL-10 supplementation has been touted as being a possible alternative treatment for CD in humans. Clinical trials have shown that recombinant human IL-10 is safe and well tolerated up to a dose o 8 μg/kg. However, to date, the results of the clinica trials have been disappointing. Although CD activity was reduced as measured by the CD activity index IL-10 supplementation did not result in significantly reduced remission rates or clinical improvements when compared to placebo. This review discusses why IL-10supplementation is not effective in CD patients currently and what can be addressed to potentially make IL-10 supplementation a more viable treatment option in the future. Based on the current research we conclude that IL-10 supplementation is not a one size fits all treatment and if the correct population of patients is chosen then IL-10 supplementation could be of benefit.

Effect of IFN-γ/IL-10 on IL-10 Receptor Expression of Human Decidual Stromal Cells in Early Pregnancy

Objective To study the role of IFN-γ/IL-10 cytokines protein expression of human decidual stromal cells（DSC） vitro. on IL-10 receptor gene and in human early pregnancy in vitro. Methods Human DSC was isolated and cultured in vitro, and the expression of IL-10R1 and IL-10R2 gene was analyzed after cells had been treated with TH2-type cytokines IL-10 and TH1-type cytokines IFN-γ within 60 rain with semiquantitative reverse transcriptase-PCR, then the influence of IL-10 and IFN-γ on expression of IL-10R protein was examined by first trimester DSC using flow cytometry. In addition, the vitality of DSC was detected by MTT. Results IL-10R1 mRNA levels of DSC treated with IL-10 （10 ng/ml） reached the peak level within 15 rain, and were significantly lower at 30 rain, then were not detected at 45 min. The expression of IL-10R1 were induced to moderate level by IFN-γ（10 ng/ml） within 30 rain, and reduced to undetected levels at 60 min. There was no significant difference of IL-10R2 expression （P〉0.05） between treated and not with the abovementioned cytokines. The IL-10R protein expression and vitality of DSC were significantly enhanced by IL-10 （10 ng/ml） and IFN-γ （10 ng/ml） which treated DSC 48 h （P〈0.05）. Coneclusion IL-10 and IFN-γ may play an important role of biologic function in early pregnancy by influencing IL-10R expression of DSC.

Lactobacilli inhibit interleukin-8 production induced by Helicobacter pylori lipopolysaccharide-activated Toll-like receptor 4

AIM： To investigate the effect of Lactobacillus bulgaricus （LBG） on the Toll-like receptor 4 （TLR4） pathway and interleukin-8 （IL-8） production in SGC-7901 cells treated with Helicobacter pyloriSydney strain 1 lipopolysaccharide （HpyloriSS1-LPS）. METHODS： SGC-7901 cells were treated with HpyloriSS1-LPS in the presence or absence of pretreatment for 1 h with viable LBG or supernatant recovered from LBG culture MRS broth （LBG-s）. Cellular lysates were prepared for Western blot with anti-TLR4, anti-transforming growth factor β-activated kinase 1 （TAK1）, anti-phospho-TAK1, anti-nuclear factor κB （NF-κB）, anti-p38 mitogen-activated protein kinase （p38MAPK）, and anti-phospho-p38MAPK antibodies. The amount of IL-8 in cell culture medium was measured by ELISA. RESULTS： H pyloriSS1-LPS up-regulated the expression of TLR4, stimulated the phosphorylation of TAKI, subsequently enhanced the activation of NF- κB and the phosphorylation of p38MAPK in a time- dependent manner, leading to augmentation of IL-8 production in SGC-7901 cells. Viable LBG or LBG-s pretreatment attenuated the expression of TLR4, inhibited the phosphorylation of TAK1 and p38MAPK, prevented the activation of NF-κB, and consequently blocked IL-8 production.CONCLUSION： H py/oriSS1-LPS induces IL-8 production through activating TLR4 signaling in SGC-7901 cells and viable LBG or LBG-s prevents H pyloriSS1-LPS-mediated IL-8 production via inhibition of the TLR4 pathway.

Interleukin-6 and ratio of plasma interleukin-6/interleukin-10 as risk factors of symptomatic lumbar osteoarthritis

AIM To determine the role of cartilage oligomeric matrix protein(COMP), interleukin(IL)-6, IL-10 and ratio of IL-6/IL-10 as risk factors of symptomatic lumbar osteoarthritis(OA) in postmenopausal women with estrogen deficiency.METHODS Case-control study had been conducted in Sanglah General Hospital from October 2015 until March 2016. The blood samples were obtained and analyzed by enzyme-linked immunosorbent assay(ELISA).RESULTS From 44 pairs of samples which divided into 44 samples as case group and 44 samples as control group showed that high level of COMP in estrogen deficiency postmenopausal women were not at risk(OR = 0.7; 95%CI: 0.261-1.751; P = 0.393) for symptomatic lumbar OA(cut-off point 0.946). Estrogen deficiency in postmenopausal women with the high level of IL-6 had 2.7 times risk(OR = 2.7; 95%CI: 0.991-8.320; P = 0.033) for symptomatic lumbar OA from the low level of IL-6(cut-off point 2.264). At lower level of IL-10, there was no risk for symptomatic lumbar OA(OR = 0.6; 95%CI: 0.209-1.798; P = 0.345) than with the higher level of IL-10(cut-off point 6.049). While the high ratio of IL-6/IL-10 level in estrogen deficiency postmenopausal women gave 3.4 times risk(OR = 3.4; 95%CI: 1.204-11.787; P = 0.011)for symptomatic lumbar OA than the low ratio of IL-6/IL-10 level(cut-off point 0.364).CONCLUSION High ratio of IL-6/IL-10 plasma level was the highest risk factor for causing symptomatic lumbar OA in postmenopausal women with estrogen deficiency.

Prognostic performance of interleukin-10 in patients with chest pain and mild to moderate coronary artery lesions an 8-year follow-up study

Background Interleukin （IL）-10, IL-6 and their ratio （IL-6/IL-10） play an important role in the risk of developing coronary artery disease, and may correlate with its outcomes. Few clinical trials have investigated the prognostic impact of these factors on long-term car- diovascular events in patients presented with chest pain. Methods A prospective study was performed on 566 patients admitted with chest pain and identified mild to moderate coronary artery lesions. 1L-10, IL-6 and IL-6/IL-10 were measured. Results A total of 511 patients com- pleted the follow-up. The median follow-up time was 74 months. Kaplan-Meier analysis demonstrated a clear increase of the incidence of major adverse cardiac events during the follow-up period in patients with below-median levels of IL-10 （P = 0.006） and above-median levels of IL-6/IL-10 （P = 0.012）. Multivariate Cox proportional hazards analysis indicated the IL-10 levels to be strong independent predictors after adjustment for underlying confounders. Conclusions Elevated IL-10 levels are associated with a more favorable long-term prognosis in patients with chest pain and mild to moderate coronary artery lesions. IL-10 could be used for early risk assessment of long-term prognosis.

Association of interleukin-10 polymorphisms with risk of irritable bowel syndrome:A meta-analysis

AIM:To clarify the current understanding of the association between interleukin-10(IL-10)polymorphisms and the risk of irritable bowel syndrome(IBS).METHODS:We searched for studies in any language recorded in PubMed,Embase and Cochrane library before August 2013.The associations under allele contrast model,codominant model,dominant model,and recessive model were analyzed.The strengths of the association between IL-10 polymorphisms and IBS risk were estimated using odds ratios(OR)with 95%confidence interval(CI).Fixed effects model was used to pool the result if the test of heterogeneity was not significant,otherwise the random-effect model was selected.RESULTS:Eight case-control studies analyzing three single-nucleotide polymorphisms rs1800870(-1082 A/G),rs1800871(-819C/T),and rs1800872(-592A/C)of the IL-10 gene,which involved 928 cases and 1363 controls,were eligible for our analysis.The results showed that rs1800870 polymorphisms were associated with a decreased risk of IBS(GG+GA vs AA:OR=0.80,95%CI:0.66-0.96),(AA+GA vs GG:OR=0.68,95%CI:0.52-0.90).Subgroup analysis revealed such association only existed in Caucasian ethnicity(AA+GA vs GG,OR=0.70,95%CI:0.55-0.89).The rs1800872 polymorphisms were associated with an increased risk of IBS in Asian ethnicity(CC vs GG:OR=1.29,95%CI:1.01-1.16).There were no associations between rs1800871 polymorphisms and the IBS risk.CONCLUSION:The results suggest that IL-10 rs1800870confers susceptibility to the risk of IBS in Caucasian ethnicity,and the rs1800872 may associate with IBS risk in Asians.However,no significant associations are found between rs1800871 and IBS risk.

Interleukin-22 receptor 1 is expressed in multinucleated giant cells:A study on intestinal tuberculosis and Crohn’s disease

BACKGROUND It is challenging to distinguish intestinal tuberculosis from Crohn’s disease due to dynamic changes in epidemiology and similar clinical characteristics. Recent studies have shown that polymorphisms in genes involved in the interleukin (IL)- 23/IL-17 axis may affect intestinal mucosal immunity by affecting the differentiation of Th17 cells. AIM To investigate the specific single-nucleotide polymorphisms (SNPs) in genes involved in the IL-23/IL-17 axis and possible pathways that affect susceptibility to intestinal tuberculosis and Crohn's disease. METHODS We analysed 133 patients with intestinal tuberculosis, 128 with Crohn’s disease, and 500 normal controls. DNA was extracted from paraffin-embedded specimens or whole blood. Four SNPs in the IL23/Th17 axis (IL22 rs2227473, IL1β rs1143627, TGFβ rs4803455, and IL17 rs8193036) were genotyped with TaqMan assays. The transcriptional activity levels of different genotypes of rs2227473 were detected by dual luciferase reporter gene assay. The expression of IL-22R1 in different intestinal diseases was detected by immunohistochemistry. RESULTS The A allele frequency of rs2227473 (P = 0.030, odds ratio = 0.60, 95% confidence interval: 0.37-0.95) showed an abnormal distribution between intestinal tuberculosis and healthy controls. The presence of the A allele was associated with a higher IL-22 transcriptional activity (P < 0.05). In addition, IL-22R1 was expressed in intestinal lymphoid tissues, especially under conditions of intestinal tuberculosis, and highly expressed in macrophage-derived Langhans giant cells. The results of immunohistochemistry showed that the expression of IL-22R1 in patients with Crohn's disease and intestinal tuberculosis was significantly higher than that in patients with intestinal polyps and colon cancer (P < 0.01). CONCLUSION High IL-22 expression seems to be a protective factor for intestinal tuberculosis. IL-22R1 is expressed in Langhans giant cells, suggesting that the IL-22/IL-22R1 system links adaptive and innate immunity.

Polymorphisms of interleukin-10 promoter are not associated with prognosis of advanced gastric cancer

AIM: To evaluate the association between of the interleukin-10 (IL-10) promoter polymorphisms and survival of advanced gastric cancer (GC) patients. METHODS: The IL-10 (-1082, rs1800896; -819, rs1800871; and-592, rs1800896) genotypes in 234 patients with advanced gastric cancer and in 243 healthy controls were determined by polymerase chain reaction-restriction fragment length polymorphism assay. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by unconditional logistic regression for the associations between IL-10 genotypes and the risk of GC. The Kaplan-Meier method with log-rank testing was used to evaluate the association between genotype and survival of the patients.RESULTS: The IL-10 -1082 G allele and GCC (-1082, -819 and -592) haplotype were associated with increased gastric cancer risks (OR 1.2, 95% CI 0.6-3.2, P = 0.007, for -1082 G allele, OR = 2.3, 95% CI, 1.2-4.1, P = 0.005, for GCC haplotype, respectively). However, none of the three IL-10 gene polymorphisms (-1082, -819 and -592) was correlated with gastric cancer survival (P > 0.05), and none of the genotypes of the three IL-10 sites was found as independent prognostic risk factors in the multivariate test. CONCLUSION: IL-10 gene promoter polymorphisms may not be associated with the prognosis of advanced gastric cancer.

Serum soluble interleukin-2 receptor levels in patients with chronic hepatitis B virus infection and its relation with antiHBc

AIM： To investigate the relationship between serum soluble interleukin-2 receptor （sIL-2R） level and anti-HBc in patients with chronic hepatitis B virus （HBV） infection. METHODS： Sera from 100 patients with chronic HBV infection and 30 healthy controls were included in this study. The patients were divided into group A [HBsAg （＋）, HBeAg （＋） and anti-HBc （＋）, n = 50] and group B [HBsAg （＋）, HBeAg （＋） and anti-HBc （-）, n = 50]. sIL-2R levels were determined using ELISA. HBV DNA and alanine aminotransferase （ALT） were also detected. RESULTS： Serum sIL-2R levels were significantly higher in patients with chronic HBV infection than in healthy controls. Moreover, serum sIL-2R levels were significantly higher in patients with HBsAg （＋）, HBeAg （＋） and antiHBc （＋） （976.56±213.51×10^3 U/L） than in patients with HBsAg （＋）, HBeAg （＋） and anti-HBc （-） （393.41±189.54 ×10^3 U/L, P〈 0.01）. A significant relationship was found between serum sIL-2R and ALT levels （P〈 0.01） in patients with chronic HBV infection, but there was no correlation between sIL-2R and HBV DNA levels. The anti-HBc status was significantly related to the age of patients （P〈 0.01）. CONCLUSION： The high sIL-2R level is related to positive anti-HBc in chronic hepatitis B patients. Positive anti-HBc may be related to T-lymphocyte activation and negative anti-HBc may imply immune tolerance in these patients.