Targeting tumour necrosis factor in the treatment of rheumatoid arthritis.

Inflammation in rheumatoid arthritis (RA) is associated with an imbalance between pro- and anti-inflammatory factors, which leads to a persistent chronic inflammatory state in the joint. Molecular studies of the physiology of the inflammatory response have identified a hierarchy of cytokine activities. The identification of this hierarchy has provided new potential therapeutic targets for the treatment of RA. At present the majority of new therapeutic agents have been developed to neutralise the activity of tumour necrosis factor-alpha (TNF alpha), a cytokine at the top of the inflammatory cascade. These agents consist of recombinant proteins that bind and neutralise TNF alpha, and they are effective in the treatment of inflammation in RA. In this review we discuss the rationale behind targeting TNF alpha, the various recombinant proteins that have been used, their clinical effectiveness, the possible adverse effects of these agents and the development of new chemical inhibitors of TNF alpha synthesis.