Matsui Kiyoshi, Tsutsui Hiroko, Nakanishi Kenji
Division of Rheumatology and Clinical Immunology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Expert Opin Ther Targets. 2003 Dec;7(6):701-24. doi: 10.1517/14728222.7.6.701.
IL-18 is a unique cytokine with prominently wide spectrum biological actions. Among these, its IFN-gamma/TNF-alpha-inducing activity primarily contributes to the development of various inflammatory diseases including inflammatory arthritis. IL-18 levels correlate with the disease activity of rheumatoid arthritis (RA) and osteoarthritis (OA). IL-18 is spontaneously released from RA synovial cells and OA chondrocytes and seems to participate in the development of the inflammatory and destructive alterations of joints via induction of TNF-alpha, a potent effector molecule. TNF-alpha, in turn, increases IL-18 expression in RA synovial cells. Recent clinical trials have revealed the efficacy of TNF-alpha in RA with a reduction in circulatory IL-18 levels. These may implicate the positive circuit between IL-18 and TNF-alpha for development of RA. As IL-18-deficient mice evade collagen-induced arthritis in a mouse RA model, therapeutics targeting IL-18 may be beneficial against RA/OA. Here, the authors review the possible roles of IL-18 in inflammatory arthritis.
白细胞介素-18（IL-18）是一种独特的细胞因子，具有显著广泛的生物学活性。其中，其诱导γ干扰素/肿瘤坏死因子-α（IFN-γ/TNF-α）的活性主要促成了包括炎性关节炎在内的各种炎性疾病的发展。IL-18水平与类风湿关节炎（RA）和骨关节炎（OA）的疾病活动度相关。IL-18由RA滑膜细胞和OA软骨细胞自发释放，似乎通过诱导强效效应分子TNF-α参与关节炎症和破坏性改变的发展。反过来，TNF-α会增加RA滑膜细胞中IL-18的表达。近期临床试验显示TNF-α对RA有效，可降低循环中IL-18水平。这些可能暗示了IL-18与TNF-α之间在RA发展过程中的正反馈回路。由于在小鼠RA模型中，IL-18缺陷小鼠可避免胶原诱导的关节炎，靶向IL-18的疗法可能对RA/OA有益。在此，作者综述了IL-18在炎性关节炎中的可能作用。
