Cytokines in the pathogenesis of rheumatoid arthritis
The imbalance between the activity of pro- and anti-inflammatory cytokines favouring induction of autoimmunity, chronic inflammation and joint damage is well known, but how cytokines are organised within a hierarchical regulatory network and which cytokines are the best targets for clinical intervention is uncertain. This review therefore examines the effector function of cytokines in the immunological processes central to the pathogenesis of rheumatoid arthritis (RA). The paper aims to try and elucidate the roles of cytokines within the complex regulatory network related to specific immunological processes including the promotion of autoimmunity, chronic inflammation and tissue destruction; and to define the functional hierarchies to identify novel opportunities to control RA and induce disease remission. The main focus is the role of cytokines in joint tissues involved in the various clinical phases of RA, but the systemic activities of cytokines released from inflamed synovia, secondary lymphoid organs and target tissues, such as interleukin (IL) 6 and tumour necrosis factor (TNF), which may result in some features of RA, are also considered. The authors conclude that as TNF inhibition is not successful in the treatment of RA and other autoimmune inflammatory disorders in all patients, inhibition of IL-6, IL-15, IL-12, IL-23, IL-18 and IL-17 could offer further therapeutic potential.