摘要:
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.Methods A 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 system Ⅱ (APACHE Ⅱ) 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.Results Compared 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-γ and TGF-β in 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-γ and TGF-β cytokines (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 than that in the survival group (P<0.05).IL-35 levels in the survival and death groups were analyzed by ROC curve with a AUC of 0.78 (P=0.03).The ~ IL-35 level was negatively correlated with the APACHE-Ⅱ score in the study group (r=-0.78,P<0.01).Conclusions The IL-35 levels in patients with sepsis and MODS is significantly higher than that in healthy controls,and negatively correlated with APACHE Ⅱ score.The level of IL-35 has an important implication for the prognosis for patients with sepsis.%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1h内取血,采用酶联免疫吸附试验(ELISA)同时检测IL-35、IL-4、IL-I0、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-y、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患者血清IL-35较健康对照组明显上升,与APACHEⅡ评分呈负相关,故其水平随APACHEⅡ评分升高而降低,IL-35水平的高低对脓毒症患者的预后有重要提示意义.