Current concept of the role of monocytes/macrophages in inflammatory bowel disease--balance of proinflammatory and immunosuppressive mediators.

Abstract Macrophages are important in providing the first line of intestinal defence against microorganisms or toxins that break the epithelial barrier, by presenting antigen to sensitised T cells and releasing a variety of cytokines and inflammatory mediators. During active states in inflammatory bowel disease, large numbers of monocytes leave the bloodstream and migrate into the inflamed mucosa and submucosa. Phenotypic studies have previously shown the presence of much more marked macrophage heterogeneity in inflammatory bowel disease mucosa than in normal mucosa. In both Crohn's disease and in ulcerative colitis, distinct macrophage populations have been found, being prominent in active disease, but absent from normal mucosa. Studies in our institution have shown that the Ca(2+)-binding proteins MRP8 and MRP14 as well as their heterocomplex MRP8/14 (27E10 epitope) are expressed in the majority of granulocytes and macrophages in active but not inactive inflammatory bowel disease. Furthermore, a strong complex MRP8/14 immunoreactivity was present in epithelial cells of the terminal ileum adjacent to ulcerative and fissuring lesions, while epithelial cells of large bowel tissues were consistently negative. In vitro studies revealed that interleukin-13, interleukin-10 and interleukin-4 strongly suppress secretion of different monocytic proteins. A combination of TH2-cytokines even at suboptimal concentrations significantly suppressed protein secretion, much more than using interleukin-13, interleukin-10 or interleukin-4 at a double concentration alone. Our morphological findings demonstrate the presence of MRP8/14 (27E10 antigen) both in monocytes/macrophages and in epithelial cells in active inflammatory bowel disease. Systemic or topical application of combined cytokine treatment might be a new effective therapeutic approach for chronic inflammatory bowel disease especially in those cases in which monocytes/macrophages lose their ability to respond, to some degree, to anti-inflammatory cytokines.