Recent developments in the immunology of inflammatory bowel disease.
Crohn's disease and ulcerative colitis are caused by excessive immune reactivity in the gut wall. Analysis of the type of immune responses ongoing in diseased gut has revealed important features which suggest that these conditions are different. In Crohn's disease tissue there is considerable evidence for an ongoing T helper cell type 1 response, with excess interleukin-12, interferon-gamma and TNF-alpha. There is circumstantial evidence in patients that this response is directed against the normal bacterial flora and definitive evidence in mouse models that T cell responses to the flora cause gut disease. In ulcerative colitis, the role of tissue damaging T cell responses in the gut mucosa is much less clear and there is more evidence that the lesion is owing to antibody-mediated hypersensitivity. Although different types of immune reactions initiate tissue injury in both Crohn's disease and ulcerative colitis, the downstream events which actually damage the tissue are the same in each condition. Elevated cytokine concentrations in the mucosa lead to the production of excess matrix degrading enzymes by gut fibroblasts, loss of mucosal integrity and ulceration. The same process also 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.
MacDonald
T T
TT
Department of Paediatric Gastroenterology, St Bartholomews and the Royal London School of Medicine and Dentistry, London, EC1A 7BE, UK.
Monteleone
G
G
Pender
S L
SL
D000818:Animals; D003093:Colitis, Ulcerative / Q000276:immunology; D003424:Crohn Disease / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004064:Digestive System / Q000276:immunology / Q000382:microbiology; D004195:Disease Models, Animal; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D018664:Interleukin-12 / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology
D016207:Cytokines; D018664:Interleukin-12