Regulation of TNF-α with a focus on rheumatoid arthritis

Cytokines and chemokines represent two important groups of proteins that control the human immune system. Dysregulation of the network in which these immunomodulators function can result in uncontrolled inflammation, leading to various diseases including rheumatoid arthritis (RA), characterized by chronic inflammation and bone erosion. Potential triggers of RA include autoantibodies, cytokines and chemokines. The tight regulation of cytokine and chemokine production, and biological activity is important. Tumor necrosis factor-alpha (TNF-alpha) is abundantly present in RA patients' serum and the arthritic synovium. This review, therefore, discusses first the role and regulation of the major proinflammatory cytokine TNF-alpha, in particular the regulation of TNF-alpha production, post-translational processing and signaling of TNF-alpha and its receptors. Owing to the important role of TNF-alpha in RA, the TNF-alpha-producing cells and the dynamics of its expression, the direct and indirect action of this cytokine and possible biological therapy for RA are described.