INTERLEUKIN-8 - CELLS OF ORIGIN IN INFLAMMATORY BOWEL-DISEASE

Neutrophils are important cellular mediators in inflammatory bowel dis ease (IBD). Interleukin (IL)8, a powerful neutrophil chemoattractant, is found in increased quantities in inflamed mucosa, but the cells of origin are uncertain. IL8 gene expression was studied by in situ hybri disation in uninflamed intestinal tissue resected for colon carcinoma (n=7) and in inflamed colonic tissue resected for IBD (n=11). Immunohi stochemistry was used to assess the phenotype of IL8 expressing macrop hages and the production of IL8 protein. Macrophages isolated from int estinal resections and lipopolysaccharide stimulated peripheral blood monocytes treated with 5-aminosalicylic acid, hydrocortisone, and cycl osporin A were examined for IL8 mRNA by northern blotting and IL8 secr etion by enzyme linked immunosorbent assay (ELISA). In all cases IL8 m RNA was detected by in situ hybridisation in macrophages and neutrophi ls adjacent to ulceration in inflamed bowel, but not detected in uninf lamed carcinoma resections. recruited CD14 positive macrophages were r esponsible for some of this IL8 expression. IL8 protein was present in the same distribution as mRNA. Epithelial cells in normal and inflame d tissue showed neither mRNA nor protein. IL8 mRNA was expressed signi ficantly more commonly by macrophages from IBD affected than from norm al mucosa, and IL8 secretion by IBD but not normal colon macrophages w as augmented significantly by lipopolysaccharide treatment, IL8 expres sion and production by lipopolysaccharide treated blood monocytes was inhibited by the therapeutic agents tested. These results show that ne utrophils and recently recruited macrophages are responsible for produ ction of IL8 in IBD, suggesting a mechanism for a continuing cycle of neutrophil attraction. Agents used therapeutically in these diseases m ay be effective in part by disrupting this cycle.