Novel therapies for Crohn's disease

Corticosteroids, 5-aminosalicylic acid (5-ASA) and antibiotics are traditio nal treatments for flare-ups of Crohn's disease and are useful in their imm ediate treatment but show few or no long-term responses. For management of steroid-dependent patients or those with refractory disease, the immunosupp ressants azathioprine, 6-mercaptopurine, methotrexate and cyclosporin help to maintain remission. However, some patients stop responding to these drug s and concerns over toxicity and neoplasia limit their use. This has led to the development of novel approaches such as immunomodulation therapy using cytokines and anticytokines. The proinflammatory cytokine tumor necrosis f actor-alpha (TNF-alpha) plays a leading role in mucosal inflammation. TNF i nhibition can be achieved with pentoxyfylline and thalidomide and also thro ugh the inactivation of TNF-alpha convertase (TACE). The antiTNF monoclonal immunoglobulin G1 (IgG1) antibody infliximab can thoroughly inactivate bot h cellular and free mucosal TNF and has been shown to be an effective thera py for refractory Crohn's disease. Other novel approaches include anti-IL-1 2, anti-interferon-gamma, antisense oligonucleotides to intercellular adhes ion molecule-1 and NF kappaB, as well as the administration of the immunore gulatory cytokines IL-10 and IL-11. (C) 2000 Prous Science. All rights rese rved.