Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
J Interferon Cytokine Res. 2011 Dec;31(12):927-40. doi: 10.1089/jir.2011.0094.
Cytokines are immune mediators that play an important role in the pathogenesis of rheumatoid arthritis (RA), an autoimmune disease that targets the synovial joints. The cytokine environment in the peripheral lymphoid tissues and the target organ (the joint) has a strong influence on the outcome of the initial events that trigger autoimmune inflammation. In susceptible individuals, these events drive inflammation and tissue damage in the joints. However, in resistant individuals, the inflammatory events are controlled effectively with minimal or no overt signs of arthritis. Animal models of human RA have permitted comprehensive investigations into the role of cytokines in the initiation, progression, and recovery phases of autoimmune arthritis. The discovery of interleukin-17 (IL-17) and its association with inflammation and autoimmune pathology has reshaped our viewpoint regarding the pathogenesis of arthritis, which previously was based on a simplistic T helper 1 (Th1)-Th2 paradigm. This review discusses the role of the newer cytokines, particularly those associated with the IL-17/IL-23 axis in arthritis. Also presented herein is the emerging information on IL-32, IL-33, and IL-35. Ongoing studies examining the role of the newer cytokines in the disease process would improve understanding of RA as well as the development of novel cytokine inhibitors that might be more efficacious than the currently available options.
细胞因子是免疫介质,在类风湿关节炎(RA)的发病机制中发挥重要作用,RA 是一种针对滑膜关节的自身免疫性疾病。外周淋巴组织和靶器官(关节)中的细胞因子环境对引发自身免疫性炎症的初始事件的结果有很强的影响。在易感性个体中,这些事件会驱动关节的炎症和组织损伤。然而,在抗性个体中,炎症事件得到有效控制,关节炎的明显体征很少或没有。人类 RA 的动物模型允许对细胞因子在自身免疫性关节炎的起始、进展和恢复阶段的作用进行全面研究。白细胞介素-17(IL-17)的发现及其与炎症和自身免疫病理学的关联改变了我们对关节炎发病机制的看法,此前我们的观点基于一个简单的 Th1-Th2 范式。本文讨论了新的细胞因子,特别是与 IL-17/IL-23 轴相关的细胞因子在关节炎中的作用。本文还介绍了新兴的关于 IL-32、IL-33 和 IL-35 的信息。正在进行的研究检查了新细胞因子在疾病过程中的作用,将有助于更好地理解 RA 以及开发可能比现有选择更有效的新型细胞因子抑制剂。