EXPRESSION OF INTERLEUKIN-8 GENE IN INFLAMMATORY BOWEL-DISEASE IS RELATED TO THE HISTOLOGICAL GRADE OF ACTIVE INFLAMMATION

Interleukin-8 (IL-8) is a potent cytokine for recruitment and activati on of neutrophils. To visualize its distribution in the intestinal muc osa and to understand better its possible role in the induction and pr omotion of inflammatory bowel disease, expression of the IL-8 gene was analyzed in resected bowel segments of 14 patients with active Crohn' s disease or ulcerative colitis. In situ hybridization with IL-8 anti- sense RNA probes revealed strong and specific signals in the histologi cally affected mucosa. The number of cells expressing IL-8 gene correl ated with the histological grade of active inflammation In accordance with tbe characteristic histological signs of active disease, IL-8-exp ressing cells were diffusely distributed over the entire affected muco sa in patients with ulcerative colitis, whereas inpatients with Crohn' s disease, IL-8-expressing cells showed a focal distribution pattern. Cells expressing IL-8 were mainly located at the base of ulcers, infla mmatory exudates on mucosal surfaces, in crypt abscesses, and at the b order of fistulae Analysis of semi-serial sections pointed to macropha ges, neutrophils, and epithelial cells as possible sources of this cyt okine in active inflammatory bowel disease. We consistently failed to detect IL-8 messenger RNA in the mucosa of uninvolved bowel segments a nd in normal-appearing control mucosa of patients with colon cancer. I n contrast, tissue specimens from two patients with acute appendicitis displayed IL-8-expressing cells in the mucosa. These results support the notion that IL-8 plays an important but nonspecific role in the pa thogenesis of inflammatory bowel disease and that the production of IL -8 messenger RNA is restricted to areas with histological signs of inf lammatory activity and mucosal destruction.