IMMUNOSUPPRESSIVE AND IMMUNOMODULATORY THERAPY FOR INFLAMMATORY BOWEL-DISEASE

Identification of the mechanisms and mediators involved in the pathogenesis of inflammatory bowel disease (IBD) has provided a sound rationale for the therapeutic use of immunosuppressive agents and has led to novel therapeutic approaches. The efficacy of traditional immunosuppressives such as the purine analogues (azathioprine/6-mercaptopurine) in both Crohn's disease and ulcerative colitis is now well established. However, the slow onset of clinical efficacy associated with purine analogues has prompted the investigation of other immunosuppressives such as cyclosporine and FK506 that have a more rapid onset of action. While early results appear promising, the exact role of these agents requires more investigation. Because of the potential for long term toxicity, many clinicians view the role of cyclosporine as an interim measure for acutely ill patients. More recent immunomodulatory approaches to IBD have been selected, not on the basis of empiric observation, but because of an improved understanding of the immunopathogenesis of these disorders. Novel approaches that are in an early phase of investigation include the modulation of cytokines and their receptors, inhibition of mucosal antigen processing and presentation, and the use of monoclonal antibodies targeted to specific mucosal effector lymphocytes.