LOCATION OF TUMOR-NECROSIS-FACTOR-ALPHA BY IMMUNOHISTOCHEMISTRY IN CHRONIC INFLAMMATORY BOWEL-DISEASE

This study determined the location and tissue density of cells immunor eactive for tumour necrosis factor alpha (TNF alpha) in intestinal spe cimens from 24 patients with chronic inflammatory bowel disease (15 wi th Crohn's disease, nine with ulcerative colitis) and 11 controls. The re was significantly increased density of TNF alpha immunoreactive cel ls in the lamina propria of both ulcerative colitis and Crohn's diseas e specimens, although the distribution of these cells differed in the two conditions. In ulcerative colitis most of the TNF alpha immunoreac tivity was seen in the subepithelial macrophages, with comparatively l ess in the deep lamina propria, while in Crohn's disease immunoreactiv e cells were distributed evenly throughout the lamina propria. Increas ed submucosal immunoreactivity was found only in Crohn's disease, in w hich TNF alpha positive macrophages tended to cluster around arteriole s and venules, often infiltrating and disrupting vascular endothelium. It is suggested that this degree of TNF alpha production probably con tributes significantly to the pathogenesis of both Crohn's disease and ulcerative colitis, by impairing the integrity of epithelial and endo thelial membranes, increasing inflammatory cell recruitment, and by pr othrombotic effects on the vascular endothelium.