Cytokine regulation of experimental intestinal inflammation in genetically engineered and T-lymphocyte reconstituted rodents.
Phenotypically similar intestinal inflammation and systemic wasting develops following overexpression or targeted deletion of several key immunoregulatory molecules and transfer of lymphocyte subsets into immunodeficient recipients. Although many of these recently described models of intestinal inflammation have not been thoroughly investigated, several consistent features are present which provide important insights into the role of cytokines in the pathogenesis of intestinal inflammation: (i) entirely distinct genetic alterations of cytokine expression and T-lymphocyte activity can lead to phenotypically similar intestinal inflammation, suggesting that human inflammatory bowel disease could have marked genetic heterogeneity; (ii) dysregulation of any of a number to immunoregulatory molecules can result in intestinal inflammation, illustrating the complexity of the mucosal immune response; (iii) active immunosuppression is critical to maintaining mucosal homeostasis; (iv) interferon-gamma and CD4+ lymphocytes, probably of the TH1 phenotype, are required for progression of chronic intestinal inflammation; (v) monokines are consistently upregulated, but tumour necrosis factor blockade is only partially protective. These models represent powerful new tools to understand better the basic mechanisms of mucosal immunoregulation and to develop novel therapeutic approaches of enhancing endogenous immunosuppressive pathways and blocking key regulatory cytokines and cells.
Division of Digestive Diseases, University of North Carolina at Chapel Hill 27599-7080, USA.
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D000818:Animals; D030801:Animals, Genetically Modified; D003092:Colitis / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D016207:Cytokines / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology*
D016207:Cytokines