Potential target of infliximab in autoimmune and inflammatory diseases

Tumour necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine produced by many cell types (blood monocytes, macrophages, mast cells and endothelial cells), that play a key role in the pathogenesis of multiple autoimmune and nonautoimmune disorders. A number of large placebo-controlled trials have shown that infliximab, a chimeric monoclonal antibody against TNF-alpha, is effective and well tolerated in patients with Crohn's disease, rheumatoid arthritis and spondiloarthritides and has become a widely used treatment for these diseases. Preliminary data suggest that several forms of vasculitis appear responsive to TNF antagonists: Behcet's disease, Churg-Strauss vasculitis, polyarteritis nodosa, and giant cell arteritis, among others. Wegener's granulomatosis and sarcoidosis, have,been shown to improve with infliximab. Polymyositis/dermatomyositis may also be responsive to TNF blockade. TNF likely plays little role in Sjogren's syndrome as evidenced by the lack of efficacy of TNF antagonists. There is a rationale for using TNF blockade even in systemic lupus erythematosus, a prototype of autoantibody-mediated disease, and a pilot study seems to confirm this potential effective approach. A number of other more rare disorders also may be responsive to TNF blockade. We here review the current and p prospective roles of infliximab in the treatment of autoimmune diseases and other conditions. (c) 2007 Published by Elsevier B.V.