IL-6/IL-6受体与类风湿关节炎关联性研究新进展  

Recent progresses of the association research on IL-6/IL-6R and rheumatoid arthritis

作　　者：苗平[1] 陆梅生 张冬青[1] 

机构地区：[1]上海交通大学医学院上海市免疫学研究所,200025 [2]上海麦柏星生物科技有限公司,201204

出　　处：《免疫学杂志》2011年第4期355-360,共6页Immunological Journal

基　　金：国家自然科学基金项目(30471593);上海市科委重点项目(07JC14033和10JC1408500);上海市科委重点学科(外科学)开放课题(S30204-K01);上海市科委自然基金项目(10ZR1426100);上海市教科委重点项目(J50207);上海市免疫学研究所项目(08-A04)

摘　　要：IL-6是一种多效性前炎症细胞因子,有多种生物活性,包括介导炎症反应,免疫反应等。IL-6在许多炎症性疾病中高表达,如RA,SLE,Crohn’s病等。IL-6的产生受多种因素的调节如NF-κB,Lin28,let-7 microRNA,IL6阳性反馈环,JunB等。IL-6受体(IL-6R)包括特异性IL-6Rα及IL-6Rβ即IL-6家族成员共有的信号转导蛋白gp130。IL-6可通过两种途径向细胞内传导信号:传统途径及反式信号途径,LMO4可参与反式信号途径的调节。IL-6/IL-6R在T、B细胞的发生中起重要作用。IL-6可抑制Th1、Treg的分化,促进Th2的分化;而且IL-6是CD4+T细胞分化为Th17细胞所必需;在B细胞中IL-6可诱导RAG基因的表达,促进抗体的产生。近年来越来越多的证据表明IL-6/IL-6R与RA存在密切关联性。RA患者血清及滑液中IL-6及sIL-6R的浓度升高,并且IL-6水平与疾病活性及临床表现密切相关,这可以解释RA患者的许多症状。因此可将IL-6信号转导途径相关的分子作为RA的治疗靶点,目前也研制出几种药物,其中之一为抗sIL-6R的人源化抗体Tocilizumab。临床试验中,该药可减轻RA患者的症状,降低疾病活性,可是也带来一定的副作用,这就限制了该药在临床中的应用。正在研制的另一种抗IL-6R的抗体可能为干预RA带来新的希望。Interleukin-6（IL-6） is a multifunctional proinflammatory cytokine that regulates inflammation and the immune response.IL-6 overexpresses in several inflammatory diseases,including RA,SLE and Crohn＇s disease etc.The production of IL-6 is regulated by many factors.For example,the NF-κB,Lin28,Let-7,and IL6 positive feedback loop,as well as Jun-B.The IL-6 receptors include IL-6Rα（the specific IL-6 receptor α） and IL-6Rβ（the common signal transduction protein gp130）.There are two ways for the IL-6 signals to be transmited into cells： conventional receptor-bound signaling and trans-signaling,in which LMO4 is involved.And IL-6 also plays an important role in the development of T cells and B cells,which can suppress the differentiation of Th1 cells,downregulate of Treg cells,and promote the differentiation of Th2 cells.Furthermore,IL-6 is necessary for the production of Th17 cells;IL-6 can also induce the expression of RAG gene and promote the secretion of antibodies in B cells.Recently,more and more evidences suggest that IL-6 and IL-6R are closely associated with RA： there are high concentrations of IL-6 and IL-6R in the serum and synovial fluid of RA;the concentration levels of IL-6 and IL-6R are closely related to disease activity and clinical manifestations,which can explain many symptoms of RA.So some molecule related to IL-6 signal transduction pathway can be used as therapeutic target in RA patients.Several drugs have developed,one of which is Tocilizumab（a humanized monoclonal antibody）.The clinic trial shows that Tocilizumab can reduce the disease activity and relief symptoms of RA patients,but it also bring some side effects,which limit the clinical application of this drug.Another anti-IL-6R antibody under developing may bring new hope for RA patients.

关 键 词：IL-6 IL-6受体 RA TOCILIZUMAB 

分 类 号：R593.22[医药卫生—内科学]