Okamoto Hiroshi, Hoshi Daisuke, Kiire Akiko, Yamanaka Hisashi, Kamatani Naoyuki
Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
Inflamm Allergy Drug Targets. 2008 Mar;7(1):53-66. doi: 10.2174/187152808784165199.
Rheumatoid arthritis (RA) is a multifactorial disease characterized by chronic inflammation of the joints. Both genetic and environmental factors are involved in the pathogenesis of joint destruction and disability. In the inflamed RA joint, the synovium is highly infiltrated by CD4+ T cells, B cells, and macrophages. Furthermore, the intimal lining becomes hyperplastic due to the increased numbers of macrophage-like and fibroblast-like synoviocytes. This hyperplastic intimal synovial lining forms an aggressive front, called pannus, which invades cartilage and bone structures, leading to compromised function and/or destruction of affected joints. RA pathology is mediated by a number of cytokines (TNF-alpha, IL-1, IL-6, IL-17, IFN gamma, etc.), chemokines (MCP-1, MCP-4, CCL18, etc.), cell adhesion molecules (ICAM-1, VCAM-1, etc.) and matrix metalloproteinases. Currently, treatment strategies targeted against TNF-alpha, IL-1 and IL-6 are available. In this review, we will summarize the use of biologics, the pros and cons of the use of biologics, and discuss on the potential molecular targets of RA.
类风湿性关节炎（RA）是一种以关节慢性炎症为特征的多因素疾病。遗传和环境因素均参与关节破坏和残疾的发病机制。在发炎的RA关节中，滑膜被CD4 + T细胞、B细胞和巨噬细胞高度浸润。此外，由于巨噬细胞样和成纤维细胞样滑膜细胞数量增加，内膜衬里增生。这种增生的内膜滑膜衬里形成一个侵袭性前沿，称为血管翳，它侵入软骨和骨结构，导致受影响关节的功能受损和/或破坏。RA病理由多种细胞因子（TNF-α、IL-1、IL-6、IL-17、IFNγ等）、趋化因子（MCP-1、MCP-4、CCL18等）、细胞粘附分子（ICAM-1、VCAM-1等）和基质金属蛋白酶介导。目前，有针对TNF-α、IL-1和IL-6的治疗策略。在本综述中，我们将总结生物制剂的使用情况、使用生物制剂的利弊，并讨论RA潜在的分子靶点。
