SYSTEM OF UNSPECIFIC DEFENSE IN CHRONIC I NFLAMMATORY BOWEL-DISEASE -PATHOPHYSIOLOGIC AND THERAPEUTIC ASPECTS

Monocytes/macrophages are a prominent feature of the inflammatory infi ltrate in inflammatory bowel disease (IBD). Progress in the developmen t of monoclonal antibodies has provided a powerful means to identify a nd study various subsets of macrophages in the intestinal mucosa. In b oth Crohn's disease and ulcerative colitis distinct macrophage populat ions have been found being prominent in active disease, but absent fro m normal mucosa. Studies of our group show that the Ca2+-binding prote ins MRP8 and MRP14 as well as their heterocomplex MRP8/14 (27E10 epito pe) can be immunolocalized in the majority of granulocytes and macroph ages in active but not inactive IBD. Serum MRP8/14 concentrations are significantly increased in patients with active IBD compared with pati ents suffering from inactive/mild disease. In vitro studies revealed t hat IL-13, IL-10 and IL-4 strongly suppress secretion of monocytic pro teins. Differential responses of monocytes and macrophages towards the inhibitory effects of TH2-cytokines can be observed in both patients with IBD and control groups. Combined treatment with TH2-cytokines may effectively suppress the response of activated monocytes/macrophages thus being of potential therapeutic benefit for patients with IBD.