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

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.