脓毒症并多器官功能不全综合征患者的新型抑制性细胞因子IL-35表达及其临床意义  

Expression and clinical significance of the novel inhibitory cytokine IL-35 in patients with sepsis and multiple organ dysfunction syndrome

作　　者：吴淡森[1] 石松菁[1] 张瑞[1] 杨火保[1] 曾永萍 郑彩罚 Wu Dansen;Shi Sonjing;Zhang Rui;Yang Huobao;Zeng Yongping;Zheng Caifa(Fujian Provincial Hospital,Department of Critical Care Medicine,350001 Fuzhou)

机构地区：[1]福建省立医院重症医学二科,福州350001

出　　处：《中华急诊医学杂志》2019年第2期175-180,共6页Chinese Journal of Emergency Medicine

基　　金：福建省自然科学基金(2015J0105);福建省医学创新课题(2014-CX-2).

摘　　要：目的通过探讨脓毒症(sepsis)并多器官功能不全综合征(multiple organ dysfunction syndrome,MODS)患者血清白细胞介素-35(IL-35)的变化规律,探讨其对疾病预后的影响。方法采用前瞻性研究方法,选择22例脓毒症并MODS患者为研究组,同时选择20例健康志愿者作为对照。于患者就诊本院1 h内取血,采用酶联免疫吸附试验(ELISA)同时检测IL-35、IL-4、IL-10、IL-17、INF-γ、TGF-β等细胞因子,及流式细胞术检测CD4^+CD25^+FOXP3^+Treg细胞表达水平,并计算急性生理学与慢性健康状况评分系统Ⅱ(APAACHEⅡ)评分,根据患者入院后28 d生存结局,比较存活组(12例)与死亡组(8例)患者之间IL-35水平的差异。采用Spearman方法分析脓毒症并MODS患者IL-35与上述指标的相关性;获得IL-35诊断脓毒症及预后判断的价值。结果与对照组相比,脓毒症并MODS患者血清IL-35水平明显增高,差异具有统计学意义(P<0.05),且IL-35水平在病程第1天开始逐步升高,尤其是在第7天的时候升高较前明显(P<0.01);在脓毒症并MODS患者中,CD4^+CD25^+FOXP3^+调节T细胞数量增加,尤其在第4天增加明显,具有统计学意义(P<0.01);且病程第1天IL-35(37.80±6.76)ng/L和CD4^+CD25^+FOXP3^+Treg细胞水平(2.09±0.32)%呈正相关(r=0.60,P<0.05);与对照组相比,脓毒症并MODS患者血清IL-10、IL-4、IL-17、INF-γ及TGF-β等细胞因子水平随着病程逐渐增高,第7天的表达量水平明显高于第1天及第4天,差异具有统计学意义(P<0.05);脓毒症并MODS患者血清IL-35水平与INF-γ、TGF-β细胞因子呈正相关(P<0.05),而与IL-10、IL-4、IL-17等细胞因子的表达无明显关系(P>0.05);死亡组患者血清IL-35水平明显低于存活组,且差异有统计学意义(P<0.05),存活组和死亡组患者血清IL-35水平进行ROC曲线分析,曲线下面积AUC=0.78(P=0.03),预测价值较好;脓毒症并MODS患者血清IL-35水平与APACHE-Ⅱ评分(8.18±3.97)呈负相关(r=-0.78,P<0.01)。结论脓毒症并MODS患�Objective To investigate the expression of interleukin-35(IL-35)in patients with sepsis and multiple organ dysfunction syndrome(MODS),and to explore its effect on disease prognosis.MethodsA prospective study was conducted.Twenty-two patients with sepsis and MODS were selected as study group,and 20 healthy volunteers were selected as controls.Blood samples of the patients and the volunteers were taken within 1 hour of the patient's visit,and cytokines,such as IL-35,IL-4,IL-10,IL-17,INF-γ,and TGF-β,were simultaneously detected by enzyme-linked immunosorbent assay(ELISA).The expression level of CD4^+CD25^+FOXP3^+Treg cells was detected by flow cytometry,and the acute physiology and chronic health status scoring systemⅡ(APACHEⅡ)was calculated.According to the survival outcome at 28 days after admission,the expression levels of IL-35 in the survival group(12 cases)and the death group(8 cases)were compared.The Spearman method was used to analyze the correlation between IL-35 level and the above indicators in patients with sepsis and MODS.ResultsCompared with the control group,the IL-35 levels were significantly increased in the study group(P<0.05),and the IL-35 levels began to increase gradually on the first day of the disease,and significantly higher on the 7th day(P<0.01).The number of CD4^+CD25^+FOXP3^+regulatory T cells increased in the study group,especially on the 4th day(P<0.01),and on the first day of the disease,the IL-35 levels were positively correlated to the number of CD4^+CD25^+FOXP3^+Treg cells(r=0.60,P<0.05).Compared with the control group,the levels of IL-10,IL-4,IL-17,INF-γand TGF-βin the study group increased gradually with the course of disease,and were significantly higher on the 7th day than those on the 1st day and the 4th day(P<0.05).The IL-35 levels in the study group were positively correlated with INF-γand TGF-βcytokines(P<0.05),whereas there was no significant relationship between the levels of IL-10,IL-4,and IL-17(P>0.05).The IL-35 level in the death group was significantly lower

关 键 词：白细胞介素-35 细胞因子 脓毒症 多器官功能不全综合征 免疫 

分 类 号：R459.7[医药卫生—急诊医学]