IMMUNOTHERAPY OF CROHNS-DISEASE

ALTHOUGH the initiating events of Crohn's disease are unknown, models of experimental colitis have provided new insights in the immunologica lly mediated pathways of mucosal inflammation. In Crohn's disease acti vated mucosal T lymphocytes produce proinflammatory cytokines within t he mucosal compartment, With this understanding, there has been a shif t in past years from the use of unspecific anti-inflammatory agents (c orticosteroids, aminosalicylates) to the use of immunomodulatory drugs (azathioprine, methotrexate), Moreover, novel strategies have been de signed for specific targets in Crohn's disease, in particular T lympho cytes and cytokines, In an open label study treatment of steroid-refra ctory Crohn's disease with anti-CD4+ antibodies was well tolerated and showed clinical benefit. However, a sustained depletion of the CD4+ c ells precluded further clinical trials. In controlled clinical studies , anti-tumour necrosis factor (TNF-alpha) antibodies induced complete remissions and few side effects were observed. One study suggested eff icacy in active Crohn's disease of recombinant interleukin-10. Long te rm treatment studies will have to answer questions about the indicatio ns for use, benefit and toxicity. Altogether, these results hold promi se for future management of Crohn's disease, where disease-modifying i nterventions and strategies that effectively maintain disease remissio n will play a key role.