CHEMOKINES IN INFLAMMATORY BOWEL-DISEASE MUCOSA - EXPRESSION OF RANTES, MACROPHAGE INFLAMMATORY PROTEIN (MIP)-1-ALPHA, MIP-1-BETA, AND GAMMA-INTERFERON-INDUCIBLE PROTEIN-10 BY MACROPHAGES, LYMPHOCYTES, ENDOTHELIAL-CELLS, AND GRANULOMAS

Peripheral blood monocytes are attracted from the circulation to sites of active inflammatory bowel disease. This study sought to determine the role of monocyte-attracting chemokines in inflammatory bowel disea se by examining the contribution of the alpha chemokine interferon-ind ucible protein-10, and the beta chemokines, macrophage inflammatory pr oteins-1 alpha and -1 beta and RANTES (Regulated on Activation, Normal T Expressed and Secreted) by using in situ hybridization and immunohi stochemistry. Resected colonic tissue was obtained from five patients with ulcerative colitis, nine patients with Crohn's disease, and six w ith uninflamed mucosa remote from resected colon cancers. In situ hybr idization by using riboprobes demonstrated that all four chemokines we re expressed by macrophages, T lymphocytes, and endothelial cells in a ctively inflamed tissue but rarely expressed in uninflamed sections fr om inflammatory bowel disease or cancer-bearing colons. The frequency of chemokine-expressing cells was significantly greater in severely in flamed than in moderately or mildly inflamed tissue. RANTES was expres sed by T lymphocytes in normal colon lamina propria, although infreque ntly. Granulomas were present in four Crohn's disease resections, and each of the chemokines was expressed by T cells and macrophages in loo sely formed granulomas. Immunohistochemistry for macrophage inflammato ry protein-1 alpha confirmed the in situ hybridization findings: prote in was associated with macrophages, T lymphocytes, and endothelial cel ls in actively inflamed colon. This study implicated a range of chemok ines known to attract monocytes and subsets of T lymphocytes in the pa thogenesis of inflammatory bowel disease and suggested significant red undancy in the generation of chemotactic signals in chronic inflammati on.