Manipulation of cytokines in the management of patients with inflammatory bowel disease

In recent years, new concepts have been formulated for the therapeutic mana gement of the intractable forms of Crohn's disease and ulcerative colitis, the two major forms of inflammatory bowel disease. These advances are based largely on new insights into the immune-inflammatory events occurring in t he gut of these patients. Analysis of the types of immune response ongoing in the inflamed intestine has revealed that in Crohn's disease there is pre dominantly a T-helper cell type 1 response, with exaggerated production of interleukin (IL)-12 and interferon (IFN)-gamma, whereas in ulcerative colit is the lesion seems more of an antibody-mediated hypersensitivity reaction. Despite these differences, downstream inflammatory events are the same in both conditions. In both Crohn's disease and ulcerative colitis mucosa, IL- 1 beta, IL-6, IL-8 and tumour necrosis factor (TNF)-alpha are produced in e xcess, and the production of free radicals accompanying the influx of nonsp ecific inflammatory cells into the mucosa is above the normal range. Strate gies aimed at inhibiting T-cell responses are therefore more relevant in Cr ohn's disease, whereas, in theory at least, inhibition of downstream inflam matory processes should be therapeutic in both Crohn's disease and ulcerati ve colitis. This review seeks to summarize studies in which anticytokine an tibodies, cytokines or cytokine-modifying agents have been used in the trea tment of either Crohn's disease or ulcerative colitis.