CYTOKINES IN INFLAMMATORY BOWEL-DISEASE

Cytokines play a central role in the modulation of the intestinal immu ne system, They are produced by lymphocytes (especially T cells of the Th1 and Th2 phenotypes) monocytes, intestinal macrophages, granulocyt es, epithelial cells, endothelial cells, and fibroblasts. They have pr oinflammatory functions [interleukin-1 (IL-1), tumor necrosis factor ( TNF), IL-6, IL-8, IL-12] or antiinflammatory functions [interleukin-1 receptor antagonist (IL-1ra), IL-1, IL-10, IL-11, transforming growth factor beta (TGF beta)], Mucosal and systemic concentrations of many p ro-and antiinflammatory cytokines are elevated in inflammatory bowel d isease (IBD). An imbalance between proinflammatory and antiinflammator y cytokines was found for the IL-1/IL-1ra ratio in the inflamed mucosa of patients with Crohn's disease, ulcerative colitis, diverticulitis, and infectious colitis, Furthermore, the inhibition of proinflammator y cytokines and tile supplementations with antiinflammatory cytokines reduced inflammation in animal models, such as the dextran sulfate col itis (DSS) model, the trinitrobenzene sulfonic acid (TNBS) model, or t he genetically engineered model of IL-10 knockout mice. Based on these findings a rationale for cytokine treatment was defined. The first cl inical trials using neutralizing monoclonal antibodies against TNF alp ha (cA2) or the antiinflammatory cytokine IL-10 have shown promising r esults, However, many questions must be answered before cytokines can be considered standard therapy for IBD.