Future trends in the treatment of rheumatoid arthritis: cytokine targets.

Recently, anti-inflammatory cytokines and cytokine-blocking agents such as monoclonal antibodies, soluble receptors and receptor antagonists have been explored as therapeutic agents for patients with rheumatoid arthritis. The anti-inflammatory cytokines interleukin 10 (IL-10), which reverses the cartilage degradation induced by antigen-stimulated mononuclear cells, and IL-4, which reduces prostaglandin production by synoviocytes, are currently being tested for their clinical efficacy. Trials with the tumour necrosis factor alpha blocking agents infliximab (monoclonal antibody) and etanercept (the fusion protein of soluble tumour necrosis factor receptors linked to human immunoglobulin) have produced improvements in clinical and laboratory measures of inflammation with mild side-effects. Trials of IL-1 blockade with recombinant human IL-1 receptor antagonist produced significant improvement of clinical parameters with mild side-effects. Blockade of IL-6, the cytokine that induces biosynthesis of acute-phase proteins, has been attempted with i.v. injections of anti-IL-6 monoclonal antibodies with improvement in clinical variables as well as reduced acute-phase proteins.