Recent developments in the immunology of inflammatory bowel disease

Crohn's disease and ulcerative colitis are caused by excessive immune react ivity in the gut wall. Analysis of the type of Immune responses ongoing in diseased gut has revealed important features which suggest that these condi tions are different. In Crohn's disease tissue there is considerable eviden ce for an ongoing T helper cell type 1 response, with excess interleukin-12 , interferon-gamma and TNF-alpha. There is circumstantial evidence in patie nts that this response is directed against the normal bacterial flora and d efinitive evidence in mouse models that T cell responses to the flora cause gut disease. In ulcerative colitis, the role of tissue damaging T cell res ponses in the gut mucosa is much less clear and there is more evidence that the lesion is owing to antibody-mediated hypersensitivity. Although differ ent types of immune reactions initiate tissue injury in both Crohn's diseas e and ulcerative colitis, the downstream events which actually damage the t issue are the same in each condition. Elevated cytokine concentrations in t he mucosa lead to the production of excess matrix degrading enzymes by gut fibroblasts, loss of mucosal integrity and ulceration. The same process als o leads to an increased production of epithelial growth factors such as KGF Keratinocyte Growth Factor by gut fibroblasts and produces the crypt cell hyperplasia characteristic of all gut inflammatory conditions.