IL-6对脓毒症小鼠调节性树突状细胞分化与功能影响的研究  

Studies on the effect of interleukin-6 on the differentiation and function of regulatory dendritic cells in sepsis mice

作　　者：王跃新[1] 刘庆阳 吴瑶[3] 董宁[3] Wang Yuexin;Liu Qingyang;Wu Yao;Dong Ning(Department of Orthopedics,Tangshan Work’s Hospital,Tangshan,Hebei 063000,China;Department of Nephrology,Coal General Hospital,Beijing 100028,China;First Affiliated Hospital of Chinese PLA General Hospital,Beijing 100048,China)

机构地区：[1]唐山市工人医院骨一科,河北唐山063000 [2]煤炭总医院肾内科,北京100028 [3]解放军总医院第一附属医院,北京100048

出　　处：《感染．炎症．修复》2018年第2期67-71,共5页Infection Inflammation Repair

基　　金：国家自然科学基金资助项目(81000847;81272140);中国博士后面上项目(201150M1530)

摘　　要：目的:探讨IL-6对脓毒症小鼠脾脏调节性树突状细胞(DCregs)的免疫调节作用。方法:85只雄性BALB/c小鼠随机分为5组:假手术组(n=5),除不行盲肠结扎穿孔(CLP)外,其余操作同模型组;CLP组和3个IL-6治疗组(n=20)均采用CLP方法制备脓毒症模型。假手术组于手术当天处死,其余4组小鼠分别于CLP模型制作后1、2、3、4 d处死,获取脾脏DC细胞和T细胞, 3个IL-6治疗组细胞分别给予IL-6(50、100、200μg/kg)体外刺激24 h,收集DC细胞和T细胞,并进一步分离和培养DCregs(CD11c-CD45RBhigh DCregs)和CD4^+T淋巴细胞,观察各组小鼠DCregs细胞比例和DCregs分泌IL-10的变化。以假手术组CD4^+T细胞为对照组,将CLP小鼠的DCregs分别和CLP小鼠CD4^+T淋巴细胞(IL-6未刺激组)、经IL-6刺激的CLP小鼠CD4^+T淋巴细胞+IL-10抗体、经IL-6刺激的CLP小鼠CD4^+T淋巴细胞+IL-10同型对照抗体混合培养24 h,观察各组CD4^+T淋巴细胞增殖及细胞培养上清中IFN-γ、IL-4水平的变化。结果:IL-6可呈剂量依赖性促进DCregs分化及促进Dcregs分泌IL-10;IL-6还抑制了CLP小鼠CD4^+T淋巴细胞增殖和诱导Th2极化,降低CLP小鼠IL-4的水平,这一作用与IL-10的分泌相关。结论:IL-6可诱导CLP小鼠DC向调节性DC细胞亚群分化并诱导IL-10的分泌,诱导CD4^+T淋巴细胞向Th2分型,从而调节机体免疫功能。To explore the immunoregulatory effect of interleukin-6(IL-6)on the regulatory dendritic cells(DCregs)in sepsis mice spleen.Methods:Eighty-five male BALB/c mice were randomly divided into 5 groups:sham control group(n=5,as the sham cecal ligation and puncture(CLP)model but no CLP),CLP group(n=20)and 3 treatment groups(20 each)with IL-6(sepsis model was replicated by CLP).Mice in the sham control group were sacrificed at 0 day,and in the other groups were sacrificed respectively at the 1st,2nd,3rd and 4th day after CLP with 5 mice at each time point.The DC cells and T cells were immediately collected from the spleen samples,and then the cells from the 3 treatment groups were stimulated in vitro with IL-6(50,100,200μg/kg,respectively)for 24 hours,and the CD11c-CD45RBhigh DCregs(DCregs)and CD4+T lymphocytes were isolated and cultured to observe the type proportion of DCregs and the level of IL-10 secreted by DCregs.The CD4+T cells in sham control group were used as the control,DCregs obtained from the CLP mice were respectively co-cultured with CD4+T lymphocyte of CLP mice,IL-6 stimulating CD4+T lymphocyte of CLP mice+IL-10 antibody,IL-6 stimulating CD4+T lymphocyte of CLP mice+IL-10 isotype control antibody for 24 hours,then the proliferation of CD4+T lymphocytes and the levels of interferon interferon-γand IL-4 in the supernatant of cell culture medium were observed.Results:With the IL-10 secretion,IL-6 promoted the DCregs differentiation and IL-10 secretion in a dose-dependent manner,inhibited the proliferation of CD4+T lymphocytes,induced the Th2 polarization and reduced the IL-4 level.Conclusions:IL-6 can induce the differentiation of DC to DCregs and the secretion of IL-10,and induce typing CD4+T lymphocytes to Th2 type,thus improve the immune activity.

关 键 词：白细胞介素-6 调节性树突状细胞 脓毒症 

分 类 号：R459.7[医药卫生—急诊医学]