Clinical significance of increased serum IL-33 levels in patients with alcoholic liver diseases

目的：探讨血清IL-33异常升高在酒精性肝病（ALD）发病中的作用及其临床意义。方法应用ELISA法检测40例酒精性肝炎、17例重症酒精性肝炎、75例酒精性肝硬化和48例健康人血清IL-33及其可溶性受体ST2（sST2）水平，分析血清IL-33水平与临床生化指标的相关性。结果酒精性肝炎、重症酒精性肝炎和酒精性肝硬化患者血清IL-33水平分别为（85.20±9.44） pg/ml、（68.70±8.14） pg/ml和（64.45±3.78） pg/ml，均显著高于健康人[（42.17±2.41）pg/ml，P＜0.001]，且酒精性肝炎患者血清IL-33水平较酒精性肝硬化患者明显升高（P＜0.05），而在重症酒精性肝炎患者和酒精性肝硬化患者不同Child-Pugh分级组间差异无显著性（P＞0.05）；酒精性肝炎、重症酒精性肝炎和酒精性肝硬化患者血清sST2水平分别为（96.75±11.30） pg/ml、（51.92±11.78） pg/ml和（75.82±6.81）pg/ml，均显著高于健康人[（43.97±3.01） pg/ml，P＜0.001]，且酒精性肝炎患者血清sST2水平较重症酒精性肝炎或酒精性肝硬化明显升高（P＜0.001或P＜0.05），而酒精性肝硬化Child-Pugh A组患者较B级或C级明显升高（P 均＜0.001）；ALD患者外周血清IL-33水平与sST2无明显相关性，IL-33水平与淋巴细胞计数（R=0.273，P＜0.01）、白蛋白（R=0.237，P＜0.01）、ALT（R=0.462，P＜0.001）、AST（R=0.387，P＜0.001）和胆碱脂酶（R=0.225，P＜0.01）水平呈显著正相关，而血清IL-33水平与中性粒细胞、总胆红素、碱性磷酸酶、总胆固醇和凝血酶原活动度水平无显著相关性。结论酒精性肝病患者血清升高的IL-33可能促进了患者免疫反应而诱导疾病的进展。Objective To explore the changes of serum IL-33 levels in patients with alcoholic liver dis-eases. Methods Serum levels of IL-33 and its soluble receptor sST2 in patients with alcoholic hepatitis(n=40), severe alcoholic hepatitis(n=17),alcoholic liver cirrhosis(n=75),and healthy individuals (n=20) were measured by ELISA. IL-33 and sST2 levels in different groups were compared and the correlation between serum IL-33 levels and the regular biochemical indexes was analyzed. Results Patients with alcoholic hepatitis,severe alcoholic hep-atitis and cirrhosis had elevated serum IL-33 levels than that in the controls [(85.20±9.44) pg/ml,(68.70±8.14) pg/ml,(64.45±3.78) pg/ml vs. (42.17±2.41) pg/ml,P<0.001 for all],while IL-33 in patients with alcoholic hepati-tis were significantly higher than that in cirrhotic patients(P<0.05);however,there was no statistical difference be-tween patients with severe hepatitis and cirrhosis with different Child-Pugh class;Serum sST2 in alcoholic hepati-tis,severe alcoholic hepatitis and cirrhosis group significantly elevated compared to that in the controls [(96.75± 11.30) pg/ml,(51.92 ±11.78) pg/ml,(75.82 ±6.81) pg/ml vs. (43.97 ±3.01) pg/ml,P<0.001 for all],while serum sST2 levels in patients with alcoholic hepatitis was higher than that in patients with severe hepatitis or cirrhosis (P<0.001 and P<0.05,respectively);in addition,serum sST2 in patients with alcoholic cirrhosis with Child-Pugh A class was significantly higher than those in cirrhotic patients with Child-Pugh B class or C class (P<0.001 for both);there was no correlation between serum IL-33 and sST2(R=0.100,P=0.180);Serum IL-33 levels in patients with alcoholic liver disease showed positive correlation with lymphocyte counts(R=0.273,P<0.01),ALB(R=0.237, P<0.01),ALT(R=0.462,P<0.001),AST(R=0.387,P<0.001)and CHE(R=0.225,P<0.01),while no significant correla-tion with neutrophils,TBIL,ALP,GGT,TC and PTA. Conclusion Elevated serum IL-33 levels might contribute to the development of alcoholic liver disease by aggravating immunological reaction.国家自然科学基金资助项目中国科技核心期刊(ISTIC)02156-15