血清β-CTx及TRACP-5b与多发性骨髓瘤骨病病情严重程度及预后关系

目的 探讨血清Ⅰ型胶原羧基端肽β特殊序列(β-CTx)及抗酒石酸酸性磷酸酶5b同工酶(TRACP-5b)与多发性骨髓瘤骨病(MMBD)病情严重程度及预后的关系。方法 回顾分析2016年1月-2020年1月收治的MMBD患者142例。通过诊治指南和影像学检查结果将患者按病情严重程度分为1、2、3、4级组,采用酶联免疫吸附法(ELISA)检测4组血清β-CTx、TRACP-5b水平,比较4组血清指标变化情况,以Spearman分析血清β-CTx、TRACP-5b与MMBD严重程度的相关性。所有患者根据生存情况分为生存组与死亡组,采用Cox回归分析影响预后的相关因素。结果 血清β-CTx、TRACP-5b水平随4组病情严重程度等级的增加而升高(P<0.05)。Spearman分析显示,血清β-CTx、TRACP-5b水平均与MMBD病情严重程度呈正相关(r=0.753、0.627,P<0.05)。142例患者截至随访时间生存98例,死亡44例,死亡组国际分期体系(ISS) Ⅲ期占比、MMBD严重程度4级占比、病理性骨折骨病类型占比、血清β2-MG、β-CTx及TRACP-5b水平较生存组更高(P<0.05)。β-CTx/TRACP-5b高、低水平的患者生存曲线差异具有统计学意义(P<0.05)。Cox回归分析显示,血清β-CTx、TRACP-5b、β2-MG水平、ISS Ⅲ期、MMBD严重程度4级、病理性骨折骨病类型是影响MMBD患者预后的危险因素(P<0.05)。结论 血清β-CTx、TRACP-5b水平随MMBD病情严重程度的增加而升高,且二者是影响MMBD预后的危险因素。     

TGF-β及其信号通路在肝脏疾病中的研究进展

转化生长因子β(transforming growth factor-β, TGF-β)在机体正常发育和动态平衡中起重要作用。TGF-β反应性失调及其下游信号通路参与许多疾病的发生、发展。目前,TGF-β及其信号通路的研究已取得一定进展,但其在肝脏疾病中的具体作用机制尚未明确。本文对TGF-β及其信号通路在肝脏疾病中的研究进展进行综述,以期为肝脏疾病的进一步研究及治疗提供更多的理论依据。     

IL-17、CRP、CysC对急性肾盂肾炎的诊断价值及患者预后不良的影响因素分析

目的 探究白细胞介素-17(IL-17)、C反应蛋白(CRP)及胱抑素C(CysC)对急性肾盂肾炎的诊断价值,并对影响患者预后不良的因素进行分析。方法 回顾性选取2020年1月到2022年12月在铜陵市人民医院急诊内科住院治疗的急性肾盂肾炎患者96例作为研究对象,设为研究组;另选取同期50名体检健康志愿者纳入对照组。比较两组的IL-17、CRP、CysC水平,并采用受试者工作特征(ROC)曲线探究其对急性肾盂肾炎的预测价值。对96例患者进行3个月随访,36例患者复发,复发率为37.50%。将36例复发患者纳入预后不良组,60例未复发患者纳入预后良好组,并探究影响患者预后的因素。结果 研究组的IL-17、CRP、CysC水平分别为(48.26±13.78)μg/L、(42.65±11.06) mg/L、(1.38±0.45) mg/L,均显著高于对照组[(19.26±1.23)μg/L、(18.56±5.56) mg/L、(0.78±0.24) mg/L],差异均有统计学意义(P<0.05)。IL-17、CRP、CysC水平诊断急性肾盂肾炎的曲线下面积分别为0.990、0.984、...     

肺腺癌患者血清IFN-γ、IL-4、IL-6水平及与预后的关系

目的 研究肺腺癌患者血清干扰素-γ(IFN-γ)、白细胞介素-4(IL-4)、白细胞介素-6(IL-6)水平,并分析其与肺腺癌患者预后的关系。方法 将本院2018年7月—2020年7月收治的86例肺腺癌作为研究组,另将同期我院体检健康者94例作为对照组。对比研究组治疗前后与对照组血清IFN-γ、IL-4、IL-6水平;比较预后不良与预后良好肺腺癌患者治疗前血清IFN-γ、IL-4、IL-6水平,并绘制受试者工作特征(ROC)曲线,分析治疗前血清IFN-γ、IL-4、IL-6水平对肺腺癌预后不良的预测价值。结果 血清IFN-γ水平研究组治疗前<研究组治疗后<对照组,IL-4、IL-6水平研究组治疗前>研究组治疗后>对照组(P<0.05)。预后不良组治疗前血清IFN-γ水平低于预后良好组,IL-4及IL-6水平明显高于预后良好组(P<0.01)。ROC曲线分析显示,血清IFN-γ、IL-4、IL-6联合预测肺腺癌预后不良的曲线下面积更高。结论 血清IFN-γ、IL-4、IL-6在肺腺癌患者中异常表达,可能与患者预后密切相关,其联合检测可为患者预后评估提供...     

IL-17、IL-23在急性脑出血患者血清中的表达及意义

目的探讨急性脑出血患者血清炎性因子IL-17、IL-23水平变化及其临床意义。方法选择2014年1月-2015年3月收治的急性脑出血患者作为实验组(136例)及同期门诊体检健康者作为对照组(120例),检测两组血清IL-17、IL-23水平;根据出血量大小,将实验组分为大量脑出血组(34例)、中等量脑出血组(38例)以及小量脑出血组(64例)。入院3个月后,根据改良的Rankin量表(mRS)评分将患者分为预后良好(91例)和预后不良(45例)。结果与对照组比较,实验组血清IL-17、IL-23水平明显升高(P0.05)。大量脑出血组IL-17、IL-23水平明显高于中量脑出血组、少量脑出血组,少量脑出血组血清IL-17、IL-23水平最低,三组间比较差异具有统计学意义(P0.05)。与预后不良组比较,预后良好组血清IL-17、IL-23水平明显降低(P0.05)。相关性分析结果显示:血清IL-17和IL-23水平呈明显正相关(r=0.386,P=0.001)。结论急性脑出血患者血清IL-17和IL-23水平明显升高,可以在一定程度上反映患者的病情,对治疗效果的评估也具有重要的作用。     

血清可溶性生长刺激表达基因2蛋白、白介素-17在经皮冠状动脉介入治疗急性非ST段抬高型心肌梗死患者预后评估中的价值研究

目的探讨可溶性生长刺激表达基因2蛋白(sST2)、白介素-17(IL-17)在行经皮冠状动脉介入治疗(PCI)治疗急性非ST段抬高型心肌梗死(NSTEMI)患者预后中的评估价值。方法我院收治的80例NSTEMI患者,依据是否发生不良心血管事件分为预后良好组和预后差组,分析PCI治疗NSTEMI患者预后的影响因素及血清sST2、IL-17水平在PCI治疗NSTEMI患者预后中的评估价值。结果预后良好组与预后差组性别、年龄、吸烟史、基础疾病类型、合并感染病变血管分类比较,差异无统计学意义(P0.05),预后良好组血清总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、sST2、IL-17水平低于预后差组(P 0.05)。sST2、IL-17水平是PCI治疗NSTEMI患者预后的高危因素(P0.05)。血清sST2联合IL-17检测诊断PCI治疗NSTEMI患者预后的曲线下面积、灵敏度、特异度、约登指数均高于两者单一检测(P0.05)。结论血清sST2、IL-17联合检测在PCI治疗NSTEMI患者预后中的诊断价值高,对合理防治方案的制定提供参考。     

血清YKL-40、IL-33、copeptin水平与急性心肌梗死患者预后的关系

目的 探讨血清甲壳质酶蛋白（YKL）-40、白介素-33(IL-33)、和肽素（copeptin）水平与急性心肌梗死患者预后的关系。方法 选择2020年9月至2021年3月秦皇岛市第一医院心内科的重症监护室（CCU）收治的200例急性心肌梗死患者作为研究对象,按照是否发生心血管不良事件将患者分为预后良好组和预后不良组。对比两组的血清YKL-40、IL-33、copeptin水平差异,采用Spearman相关性分析分析血清YKL-40、IL-33、copeptin水平与急性心肌梗死患者预后的关系,采用多因素Logistic回归分析急性心肌梗死患者预后不良的独立影响因素,绘制受试者工作特征曲线（ROC）评估血清YKL-40、IL-33、copeptin水平对急性心肌梗死患者预后不良的预测价值。结果 预后良好组的血清YKL-40、IL-33、copeptin水平均低于预后不良组,差异具有统计学意义（t=7.788、5.415、4.534,P<0.05）。Spearman相关分析结果表明,血清YKL-40、IL-33、copeptin水平与心肌梗死患者预后不良发生呈正相关（r=0.450...     

血清脑钠肽、超敏C反应蛋白、肌酸激酶同工酶水平与经皮冠状动脉介入治疗术后患者预后的相关性

目的探讨急性心肌梗死患者经皮冠状动脉介入治疗(PCI)后血清脑钠肽(BNP)、超敏C反应蛋白(hs-CRP)、肌酸激酶同工酶(CK-MB)水平与近期预后的相关性。方法选取行PCI术的182例急性心肌梗死患者为研究对象,根据术后3个月内是否发生心血管不良事件将其分为预后不良组58例和预后良好组124例。采用酶联免疫吸附(ELISA)法检测患者血清BNP、hs-CRP、CK-MB水平;分析预后不良患者血清BNP、hs-CRP、CK-MB水平;分析血清BNP、hs-CRP、CK-MB水平对急性心肌梗死PCI后预后不良的预测价值;分析影响PCI患者术后预后不良的因素。结果预后不良组血清BNP、hs-CRP、CK-MB水平高于预后良好组,差异有统计学意义(P 0.05)。预后不良患者血清BNP与hs-CRP、CK-MB水平呈正相关(r=0.527,P 0.05; r=0.541,P 0.05),CK-MB与hs-CRP呈正相关(r=0.511,P 0.05)。血清BNP、hs-CRP、CK-MB及3者联合预测急性心肌梗死PCI后预后不良的曲线下面积(AUC)分别为0.872、0.763、0.921、0.949,特异性分别为87.9%、82.3%、94.4%、93.5%,敏感度分别为74.1%、63.8%、81.0%、87.9%。BNP、CK-MB是影响急性心肌梗死患者PCI后预后不良的独立危险因素(P 0.05)。结论血清BNP、hs-CRP、CK-MB对急性心肌梗死患者PCI后预后不良有一定的预测作用。     

血清FGF-21 IL-13 sVEGFR-2与急性心力衰竭患者短期预后的关系

目的 探讨血清成纤维细胞生长因子-21(FGF-21)、白细胞介素-13(IL-13)、可溶性血管内皮生长因子受体-2(sVEGFR-2)水平与急性心力衰竭患者短期预后的相关性。方法 选取2019年1月至2020年12月在我院接受治疗的急性心力衰竭患者136例作为心力衰竭组。选取同期在我院健康体检者80例作为健康对照组。采用ELISA法检测血清FGF-21、IL-13、sVEGFR-2水平。随访1年，根据急性心力衰竭患者有无不良心血管事件发生分为预后良好组和预后不良组，并分析影响患者1年内临床结局的危险因素。采用ROC曲线，分析FGF-21、IL-13、sVEGFR-2对急性心力衰竭患者预后不良的诊断效能。结果 心力衰竭组血清FGF-21、IL-13高于健康对照组[FGF-21(pg/mL):74.81±16.29 vs. 19.37±5.11, IL-13(pg/mL):5.14±1.23 vs.1.62±0.54,P<0.001]、sVEGFR-2低于健康对照组(ng/mL:6.30±1.57 vs.15.18±4.29,P<0.05)。预后不良组血清FGF-21、IL...     

血清脂蛋白α、胱抑素-C和尿酸检测对早期糖尿病肾病的诊断价值

目的 分析脂蛋白α[LP(α)]、血清胱抑素-C(Cys-C)和尿酸(UA)检验在早期糖尿病肾病(DN)诊断中的应用价值。方法 回顾性分析2020年1月至2021年8月在葫芦岛市中心医院确诊的2型糖尿病(T2DM)患者150例,根据尿白蛋白肌酐比值(UACR)分组,即正常白蛋白尿(NA)组50例(UACR 0~3 mg/mmol),微量白蛋白尿(MA)组51例(UACR 3~29 mg/mmol)和临床白蛋白尿(CA)组49例(UACR>30 mg/mmol),检验并比较3组一般临床资料、相关临床指标及血清LP(α)、Cys-C和UA水平,采用Pearson直线相关及Logistic回归分析各指标与DN的关系,采用受试者工作特征(ROC)曲线评估各指标对DN 的诊断价值。结果 3组收缩压、舒张压差异有统计学意义(P<0.05);UACR、血肌酐(SCr)、肾小球滤过率(eGFR)、空腹血糖(FPG)、糖化血红蛋白(HbA₁c)、Cys-C、UA、LP(α)差异有统计学意义(P<0.05)。与NA组相比,MA组的LP(α)的水平升高最明显,差异有统计学意义(P<0.05)。Pearson相关性分析显示,血清Cys-C、UA、LP(α)与UACR、SCr均呈正相关,与eGFR呈负相关;Logistic回归分析表明,Cys-C和LP(α)是早期 DN 的独立危险因素(P<0.05);ROC曲线分析结果显示,血清Cys-C和LP(α)对早期DN有较高的的诊断价值。结论 血清LP(α)、Cys-C和UA均可反映糖尿病患者肾损伤的程度,其中LP(α)和Cys-C是早期DN的独立危险因子,三者联合诊断准确度最高,对早期预测DN发生具有较高的诊断效能。     

Serum levels of inhibitory costimulatory molecules and correlations with levels of innate immune cytokines in patients with pulmonary tuberculosis

ObjectiveTo analyze serum levels of inhibitory costimulatory molecules and their correlations with innate immune cytokine levels in patients with pulmonary tuberculosis (PTB).MethodsData for 280 PTB patients and 280 healthy individuals were collected. Serum levels of immune molecules were measured using ELISA. Univariate, multivariate, subgroup, matrix correlation, and receiver operating characteristic curve analyses were performed.ResultsHost, environment, lifestyle, clinical features, and medical history all influenced PTB. Serum levels of soluble programmed death ligand 1 (sPD-L1), soluble T-cell immunoglobulin- and mucin-domain–containing molecule 3 (sTim-3), soluble galectin-9 (sGal-9), interleukin (IL)-4, and IL-33 were significantly higher in patients with PTB, while levels of IL-12, IL-23, IL-18, and interferon (IFN)-γ were significantly lower. Serum levels of sTim-3 were higher in alcohol users. Levels of sTim-3 were negatively correlated with those of IL-12. Levels of IL-12, IL-23, and IL-18 were positively correlated with those of IFN-γ, while levels of IL-12 were negatively correlated with those of IL-4. The areas under the curve of sPD-L1, sTim-3, sGal-9, IL-12, IL-23, IL-18, IFN-γ, IL-4, and IL-33 for identifying PTB were all >0.77.ConclusionsInhibitory costimulatory molecules may be targets for controlling PTB. Immune molecules may be helpful for diagnosis of PTB.     

创伤患者血清白细胞介素33和可溶性抑癌蛋白2水平与创伤的程度及预后关系

目的：研究创伤患者血清中白细胞介素33（interleukin 33, IL-33）及其受体可溶性抑癌蛋白2（soluble suppression of tumorigenicity, sST2）水平的变化,并分析两者与患者的创伤严重度及预后间的关系。方法：根据创伤严重度评分(injury severity score, ISS)将67例患者分为轻度创伤组（ISS<20分）和重度创伤组（ISS≥20分）,并选同期30名健康体检者作为健康对照组,分别于创伤后4 h、24 h、72 h、7 d等时间点抽取外周静脉血,应用酶联免疫吸附试验检测血清IL-33和sST2水平,分别比较3组间各时间点的血清IL-33和sST2水平,并比较28 d内患者的病死率;同时比较存活者与死亡者各时间点血清IL-33和sST2水平,应用受试者工作特征（receiver operating characteristic, ROC）曲线选取最佳临界值,评估创伤后血清IL-33和sST2水平预测患者死亡的价值。结果：重度创伤患者创伤后4 h、24 h血清IL-33和sST2水平均高于轻度创伤患者[IL-33,（38.75±28.43） pg/mL比（19.62±9.98） pg/mL,（42.31±37.37） pg/mL比（23.47±13.42） pg/mL,（P<0.05）;sST2,（6.50±3.74） ng/mL比（4.89±2.40） ng/mL,（8.35±2.69） ng/mL比（6.78±3.22） ng/mL,（P<0.05）];死亡患者创伤后24 h至7 d的血清IL-33和sST2水平显著高于存活患者（P<0.01）,创伤后24 h血清IL-33和sST2水平的ROC曲线下面积分别为0.799（P=0.003）和0.751（P=0.012）,最佳临界值分别为15.27 pg/mL和10.99 ng/mL,其预测死亡的灵敏度分别为100%和70%,特异度分别为64%和83%。结论：创伤患者的血清IL-33、sST2水平升高与创伤的程度重及近期预后不良相关,创伤后24 h血清IL-33 和sST2水平可能作为预测创伤患者近期预后的生物标志物。     

The role of peroxisome proliferator-activated receptor gamma and adiponectin in children with Kawasaki disease

ObjectiveTo investigate the relationship between peroxisome proliferator-activated receptor gamma (PPARγ) mRNA, serum adiponectin (ADP) and lipids in paediatric patients with Kawasaki disease (KD).MethodsThis prospective study enrolled paediatric patients with KD and grouped them according to the presence or absence of coronary artery lesions (CAL). A group of healthy age-matched children were recruited as the control group. The levels of PPARγ mRNA, serum ADP and lipids were compared between the groups. Receiver operating characteristic (ROC) curve analysis was undertaken to determine if the PPARγ mRNA level could be used as a predictive biomarker of CAL prognosis.ResultsThe study enrolled 42 patients with KD (18 with CAL [CAL group] and 24 without CAL [NCAL group]) and 20 age-matched controls. PPARγ mRNA levels in patients with KD were significantly higher than those in the controls; but significantly lower in the CAL group than the NCAL group. ROC curve analysis demonstrated that the PPARγ mRNA level provided good predictive accuracy for the prognosis of CAL. There was no association between PPARγ, ADP and lipid levels.ConclusionThere was dyslipidaemia in children with KD, but there was no correlation with PPARγ and ADP. PPARγ may be a predictor of CAL in patients with KD with good predictive accuracy.     

Profile of serum cytokine concentrations in patients with gouty arthritis

ObjectiveThis study aimed to analyze the changes in serum inflammatory cytokines and anti-inflammatory cytokines in patients with gouty arthritis (GA).MethodsThe clinical data and serum samples in patients with gouty arthritis and those in healthy volunteers were collected in China-Japan Friendship Hospital from July 2018 to January 2019. Serum cytokine concentrations in patients with GA and volunteers (controls) were determined by a chemiluminescence method. The differences in cytokine concentrations were compared between the two groups.ResultsConcentrations of serum interleukin-1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), IL-6, IL-8, and IL-4 were significantly higher in patients with acute GA than in controls. Serum concentrations of IL-1ß, TNF-α, IL-6, IL-8, and immunoglobulin E in patients with remission of GA were significantly lower, whereas concentrations of IL-10 and interferon-γ were significantly higher, compared with those in patients with acute GA.ConclusionThis study shows that serum concentrations of IL-1ß, TNF-α, IL-6, IL-8, and IL-4 are significantly elevated in patients with GA, and may be involved in the pathogenesis of GA.     

Exploring potential serum levels of Homocysteine,interleukin‐1 beta,and apolipoprotein B 48 as new biomarkers for patients with ischemic stroke

BackgroundStroke is the second leading cause of death worldwide with heterogeneous characteristics. The subtypes of stroke are due to different pathophysiological regulations and causes. This study aimed to investigate the correlation of serum levels of apolipoprotein B 48, interleukin‐1β and Homocysteine with BMI in patients with ischemic stroke (IS).MethodsOver one hundred controls (120) and an equal number of IS patients, including 31 women and 89 men, were recruited to participate in the case‐control study conducted at Imam Reza Hospital (Tabriz, Iran) from February 2019 to March 2020. We measured serum levels of apolipoprotein B 48, interleukin‐1β, and Homocysteine. Receiver operating characteristic analysis (ROC) was performed to evaluate the diagnostic value of these indices in patients and control groups.ResultsThe mean serum levels of apolipoprotein B 48, interleukin‐1β, and Homocysteine, were significantly increased in the experimental group compared to the control group with a p‐value of 0.001. The ROC curve analysis showed that the area under the curve for apo B48, IL −1β, hs‐CRP, and Homocysteine serum levels were 0.94, 0.98, 0.99, and 1, respectively.ConclusionsThe results of our current study show that the determination of serum levels of apolipoprotein B 48, interleukin‐1β, and Homocysteine can potentially be used to monitor and diagnose IS patients. However, there was no statistically significant correlation between serum levels of apolipoprotein B 48, interleukin 1β and Homocysteine and BMI in the patient group. However, there was a statistically significant inverse correlation between serum levels of high‐sensitivity C‐reactive protein (hs‐CRP) and BMI in the patient group.     

Transforming Growth Factor-��1 and Incident Type 2 Diabetes: Results from the MONICA/KORA case-cohort study, 1984�C2002

OBJECTIVE

Subclinical inflammation leads to insulin resistance and β-cell dysfunction. This study aimed to assess whether levels of circulating transforming growth factor-β1 (TGF-β1)—a central, mainly immunosuppressive, and anti-inflammatory cytokine—were associated with incident type 2 diabetes.

RESEARCH DESIGN AND METHODS

We measured serum levels of TGF-β1 from 460 individuals with and 1,474 individuals without incident type 2 diabetes in a prospective case-cohort study within the population-based MONICA (MONItoring of Trends and Determinants in CArdiovascular Disease)/KORA (Cooperative Health Research in the Region of Augsburg) cohort.

RESULTS

Elevated TGF-β1 concentrations were associated with higher, not lower, risk for type 2 diabetes (age-, sex-, and survey-adjusted hazard ratios [95% CI] for increasing TGF-β1 tertiles: 1.0, 1.08 [0.83–1.42], and 1.41 [1.08–1.83]; P_{for trend} = 0.012). Adjustment for BMI and metabolic and lifestyle factors had virtually no impact on the effect size.

CONCLUSIONS

Elevated serum concentrations of the cytokine TGF-β1 indicate an increased risk for type 2 diabetes. TGF-β1 may be upregulated to counterbalance metabolic and immunological disturbances preceding type 2 diabetes.Subclinical inflammation represents one important mechanism in the development of insulin resistance and β-cell dysfunction, and a systemic proinflammatory state is associated with increased risk for type 2 diabetes (1). However, data on anti-inflammatory immune mediators are scarce. So far, adiponectin remains the only immune mediator for which increased circulating levels indicate a reduced risk for type 2 diabetes and for which a protective effect is biologically plausible (2–4). Transforming growth factor-β1 (TGF-β1) is an interesting candidate in this context because it is a critical regulator of the immune system with mainly immunosuppressive effects (5). In addition to effects on T-cells, TGF-β1 inhibits or reverses the activation of macrophages by interfering with signaling via toll-like receptor–dependent pathways and downregulating central effector mechanisms of the innate immunity such as lipopolysaccharide-induced production of proinflammatory cytokines, reactive oxygen species, and reactive nitrogen species (6,7).Recent data on interleukin (IL)-1 receptor antagonist (IL-1Ra) from the Whitehall II study led to the hypothesis that the immunological changes before type 2 diabetes do not only include upregulation of proinflammatory mediators but also of anti-inflammatory cytokines—presumably an attempt to counterbalance subclinical inflammation (8). We tested this hypothesis in the large, population-based MONICA (MONItoring of Trends and Determinants in CArdiovascular Disease)/KORA (Cooperative Health Research in the Region of Augsburg) case-cohort study by investigating the association between TGF-β1 serum levels and incident type 2 diabetes.     

人脐带和胎盘间充质干细胞细胞因子分泌的比较研究

目的 探索人脐带间充质干细胞（UC-MSC）与胎盘间充质干细胞（P-MSC）细胞因子的分泌情况。方法 分离并培养UC-MSC和P-MSC,流式细胞术检测间充质干细胞（MSC）的表面标志物,油红O、硝酸银和茜素红S染色检测MSC的成脂、成骨分化能力。收集条件培养基,用芯片检测细胞因子的表达情况。通过ELISA及实时PCR...     

Serum IL‐36 cytokines levels in type 2 diabetes mellitus patients and their association with obesity,insulin resistance,and inflammation

BackgroundThe interleukin (IL)‐36 cytokines include IL‐36α, IL‐36β, IL‐36γ, and IL‐36Ra. Little was known about their roles in type 2 diabetes mellitus (T2DM).MethodsThe study included 40 T2DM patients and 42 healthy control subjects. The anthropometric and biochemical measurements were performed using automatic biochemical analyzer, high‐performance liquid chromatography, and electrochemiluminescence immunoassay. Circulating IL‐36α, IL‐36γ, IL‐36Ra, and IL‐17 levels were determined by enzyme‐linked immunosorbent assay.ResultsSerum IL‐36α, IL‐36γ, and IL‐17 levels in T2DM patients were significantly higher than those in controls, whereas serum IL‐36Ra levels in T2DM patients were lower. Correlation analysis showed that serum IL‐36α was positively correlated with high sensitivity C‐reactive protein. Serum IL‐36α was negatively correlated with IL‐36Ra. Serum IL‐17 was negatively correlated with low‐density lipoprotein cholesterol.ConclusionsThis study demonstrated that T2DM patients displayed increased IL‐36α and IL‐36γ expression and decreased IL‐36Ra expression. Moreover, the inflammatory cytokine levels were directly proportional to the inflammation and blood lipid levels. Our results suggest that IL‐36 cytokines may be a new target for the diagnosis or treatment of T2DM.     

Nonredundant Roles of IL-10 and TGF-�� in Suppression of Immune Responses to Hepatic AAV-Factor IX Gene Transfer

Hepatic gene transfer using adeno-associated viral (AAV) vectors has been shown to efficiently induce immunological tolerance to a variety of proteins. Regulatory T-cells (Treg) induced by this route suppress humoral and cellular immune responses against the transgene product. In this study, we examined the roles of immune suppressive cytokines interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) in the development of tolerance to human coagulation factor IX (hF.IX). Interestingly, IL-10 deficient C57BL/6 mice receiving gene transfer remained tolerant to hF.IX and generated Treg that suppressed anti-hF.IX formation. Effects of TGF-β blockade were also minor in this strain. In contrast, in C3H/HeJ mice, a strain known to have stronger T-cell responses against hF.IX, IL-10 was specifically required for the suppression of CD8⁺ T-cell infiltration of the liver. Furthermore, TGF-β was critical for tipping the balance toward an regulatory immune response. TGF-β was required for CD4⁺CD25⁺FoxP3⁺ Treg induction, which was necessary for suppression of effector CD4⁺ and CD8⁺ T-cell responses as well as antibody formation. These results demonstrate the crucial, nonredundant roles of IL-10 and TGF-β in prevention of immune responses against AAV-F.IX-transduced hepatocytes.