The Role of Chemokines in the Pathogenesis of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic, multisystem autoimmune disease characterized by persistent accumulation of leukocytes in the synovial compartment. The influx of the leukocytes is important as a critical step in the pathogenesis of RA. Chemotactic cytokines (chemokines) play a critical role in the pathogenesis of RA not only by inducing the migration of inflammatory cells but also by enhancing the production of inflammatory mediators and angiogenesis. The production of chemokines is regulated by proinflammatory cytokines such as tumor necrosis factor-α and interleukin-6 produced in the inflamed joint suggesting that the efficacy of anti-cytokine therapy is mediated at least partly by the reduction of chemokine production. Th1- type T cells have a role in the joint inflammation of RA because Th1-related chemokine receptors are predominantly expressed on RA synovial tissue T cells. The present review summarizes current knowledge on the role of chemokines and their receptors in the pathogenesis of RA. The authors also review the important relevance of chemokines for therapeutic intervention.