Study for molecular and gene therapy of rheumatoid arthritis by targeting IL-6 signal transduction.

1. 研究了抗白细胞介素-6受体抗体（anti-IL-6R Ab）对小鼠及类似胶原诱导的关节炎和关节破坏的抑制作用。人源化抗il - 6r抗体被证实对难治性类风湿关节炎（RA）患者有效，从而证实IL-6在RA病理中起重要作用。这也表明IL-6信号阻断可以成为治疗ra的新方法。可溶性IL-6R （sIL-6R）存在时，IL-6抑制滑膜细胞的生长。tnf α诱导的IL-6可能是tnf α诱导的ra滑膜细胞增殖的负反馈因子。IL-6阻断的治疗效果是通过消除穿透RA滑膜组织的炎症细胞，并通过抑制血管生成和破骨细胞形成。STATs诱导的STATs抑制剂-1及其家族分子SSI-3作为胞浆内IL-6信号的负反馈因子可能参与了ra的慢性炎症状态。这些结果提示，基于RA的病理生理机制，阻断IL-6信号通路可能成为治疗RA的新途径。

1. Inhibitory effects of anti-interleukin-6 receptor antibody (anti-IL-6R Ab) against murine and similar collagen-induced arthritis and joint destruction were elucidated.2. Humanized anti-IL-6R Ab was proven to be effective to patients with refractory rheumatoid arthritis (RA) and thus confirming that IL-6 plays a major role in the RA pathology. It also shows IL-6 signal blocking can be a new therapy for RA.3. IL-6 in the presence of soluble IL-6R (sIL-6R) inhibits the growth of synovial cells. TNFα-induced IL-6 can be a negative feedback factor of TNFα-induced synovial cell proliferation in RA.4. Therapeutic effects of IL-6 blockade were through elimination of inflammatory cell penetrating the RA synovial tissue and also through inhibition of angiogenesis and osteoclast formation.5. STATs-induced STATs inhibitor-1 and its family molecule SSI-3 as negative feed back factors of intracytoplasmic IL-6 signaling may be involved in the chronic inflammatory status of RA.6. These results indicate the possibility of new therapeutic approach for RA by blocking IL-6 signaling based on the pathophysiology of RA.