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The precise aetiology of chronic inflammatory bowel disease (IBD) has remained elusive despite many years of investigation. Both Crohn’s disease and ulcerative colitis are characterised by chronic inflammation of the gastrointestinal tract, but the regions of intestine that can be affected and the histopathological features are quite different between the two forms of IBD. It has been hypothesised that the persistent intestinal inflammation seen in either case is likely to be the result of increased or aberrant immunological responsiveness to normal constituents of the gut lumen, or an overall immune dysregulation and imbalance. Are cytokines responsible for tipping the balance?
CYTOKINE DEFICIENCY CAN LEAD TO IBD SYMPTOMS IN MICE
The recent establishment of experimental animal models for studying the pathogenesis of intestinal inflammation has provided some insight into potential disease mechanisms and has had particular impact within the mucosal immunology field. The advent of genetically targeted mice bearing modified or disrupted immune systems, and the observation that spontaneous development of IBD is a prominent feature in many of these mice lacking T cells or cytokines, is highly suggestive that an immune imbalance is a critical factor in IBD pathogenesis.
IBD arises spontaneously in mice deficient for αβ+ T cells and in mice deficient for either Th1 or Th2 regulatory cytokines, such as interleukin (IL) 2 or IL-10.1-4 The fact that mice deficient in either one of the contrary Th1 or Th2 type cytokines are equally susceptible to developing inflammation of the intestinal tract is hard to reconcile, but it tells us that the mucosal microenvironment is an exquisitely regulated system. Disrupting the homoeostatic cytokine balance in any way might thus lead to the development of an aberrant or uncontrolled inflammatory response in the gut.
HUMAN IBD CAN BE ASSOCIATED WITH INCREASED CYTOKINE CONCENTRATIONS
Although there is sufficient evidence from the mouse models to indicate that abrogation of regulatory cytokines can lead to intestinal inflammation, there is not …
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