The roles of interleukin-6 in the pathogenesis of rheumatoid arthritis.
The roles of interleukin-6 in the pathogenesis of rheumatoid arthritis.
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DOI：
10.1155/2011/765624
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Mihara M
中科院分区：
文献类型：
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作者：
Hashizume M;Mihara M
多项临床研究表明，人源化的抗白细胞介素6受体抗体抗cilizumab(TCZ)可改善类风湿关节炎(RA)的临床症状，防止关节破坏的进展。然而，IL-6阻断导致RA改善的确切机制尚不清楚。IL-6通过诱导新生血管、炎性细胞浸润和滑膜增生促进滑膜炎的发生。IL-6通过在滑膜细胞中诱导RANKL诱导破骨细胞形成，通过在滑膜细胞和软骨细胞中产生基质金属蛋白酶(MMPs)而导致软骨退化，从而导致骨吸收。此外，IL-6通过改变Th17细胞和Treg之间的平衡参与自身免疫。IL-6还作用于改变血液中的脂质浓度，并诱导产生导致缺铁性贫血的海普西丁。综上所述，IL-6在RA的发病机制中起主要作用，目前的证据表明阻断IL-6对RA患者是一种有益的治疗方法。
Several clinical studies have demonstrated that the humanized anti-interleukin-6 (IL-6) receptor antibody tocilizumab (TCZ) improves clinical symptoms and prevents progression of joint destruction in rheumatoid arthritis (RA). However, the precise mechanism by which IL-6 blockade leads to the improvement of RA is not well understood. IL-6 promotes synovitis by inducing neovascularization, infiltration of inflammatory cells, and synovial hyperplasia. IL-6 causes bone resorption by inducing osteoclast formation via the induction of RANKL in synovial cells, and cartilage degeneration by producing matrix metalloproteinases (MMPs) in synovial cells and chondrocytes. Moreover, IL-6 is involved in autoimmunity by altering the balance between Th17 cells and Treg. IL-6 also acts on changing lipid concentrations in blood and on inducing the production of hepcidin which causes iron-deficient anemia. In conclusion, IL-6 is a major player in the pathogenesis of RA, and current evidence indicates that the blockade of IL-6 is a beneficial therapy for RA patients.