Potential therapeutic role for cytokine or adhesion molecule manipulation in Crohn's disease: in the shadow of infliximab?

BACKGROUND: Inappropriate activation of the intestinal immune system leading to a persistent inflammatory response is implicated in the pathogenesis of both Crohn's disease and ulcerative colitis. Various cytokines and cell surface molecules expressed by immunologically active cells are involved and are potential targets for intervention. To date the most effective biological agent has proved to be infliximab, but many other possibilities are being considered actively. STUDIES CONSIDERED: Use of the immunoregulatory cytokines IL-10 and IL-11, and of antagonists to IL-12, IL-15 and IL-18, to integrins, and to ICAM-1 are considered. RESULTS AND
CONCLUSION: IL-10 and the anti-integrin natalizumab are currently best evaluated. Both are effective, but neither is yet a direct competitor for infliximab in Crohn's disease, and there is no strong evidence in ulcerative colitis. These agents have considerable potential which, in combination with new delivery systems (perhaps taking into account some form of genetic engineering), hold great promise.