THE CENTRAL ROLE OF CHEMOKINES (CHEMOTACTIC CYTOKINES) IN THE IMMUNOPATHOGENESIS OF ULCERATIVE-COLITIS AND CROHNS-DISEASE

The final composition of leukocytes present in a site of inflammation in response to chemokine stimulation and activation may depend on both the nature of the secreted chemokines as well as the relative express ion of the multitude of specific chemokine cell surface receptors on m any different cell types. Because related receptors with different aff inities and cross-reactive binding capabilities are present on each ty pe of leukocyte, relative differences in receptor distribution and rec eptor affinity for specific chemokines may significantly influence whi ch cells are ultimately attracted to and activated by each individual chemokine. Production of IL-8, MCP-1, and ENA-78 by endothelial cells, LPMNC, and epithelial cells in IBD could establish a chemotactic grad ient capable of influencing the increased migration of monocytes/macro phages, granulocytes, and lymphocytes from the blood stream through th e endothelium into both the mucosa and submucosa during chronic IBD. T he ability of chemokines to induce chemotaxis, leukocyte activation, g ranule exocytosis, increased production of metalloenzymes, and up-regu lation of respiratory burst activity indicates that there may be a var iety of different mechanisms by which chemokines could markedly increa se chronic inflammation and chronic intestinal tissue destruction in I BD.