High endothelin-1 immunoreactivity in Crohn's disease and ulcerative colitis

Both immunological hypersensitivity and vascular abnormalities have been implicated in the pathogenesis of inflammatory bowel disease. In an attempt to link the two hypotheses, we sought evidence of local production of endothelin-1, a potent vasoconstrictor, in patients with Crohn's disease and ulcerative colitis. An immunohistochemical method was used to detect endothelin-1 in tissue samples from sixteen Crohn's disease patients, nine ulcerative colitis patients, and thirteen controls. In the controls, positively staining cells were infrequent in both lamina propria (mean 0.9% of total cells, 95% confidence interval 0.1-1.7%) and submucosa (2.3%, 0.4-4.1%). The percentage of endothelin-immunoreactive cells was significantly higher in the two disease groups than in the controls. Among the Crohn's disease patients, there were more immunoreactive cells in the submucosa than in the lamina propria (19.1%, 15.2-22.1% vs 12.3%, 8.1-16.5%; p less than 0.001), whereas the converse was true for the ulcerative colitis group (8.6%, 1.1-16.1% vs 24.4%, 14.1-34.6%; p less than 0.001). Immunoreactive macrophage aggregates around submucosal blood vessels were common in samples from Crohn's disease patients. Endothelin concentrations, measured by radioimmunoassay, in supernatants of homogenised tissue samples were significantly higher in Crohn's disease and ulcerative colitis than in controls. We suggest that local endothelin production by inflammatory cells may contribute to vasculitis in chronic inflammatory bowel disease by inducing intestinal ischaemia through vasoconstriction.