Use of coculture of colonic mucosal biopsies to investigate the release of eicosanoids by inflamed and uninflamed mucosa from patients with inflammatory bowel disease

Abstract

Eicosanoid production was measured in cultured biopsies of colonic mucosa from control patients, with the irritable bowel syndrome, and from patients with proctosigmoiditis and with colonic Crohn's disease. Cultured inflamed colonic mucosa from patients with proctosigmoiditis and Crohn's disease produced more prostaglandin E2 and leukotrienes C4 than control tissues. In addition, eicosanoid production by macroscopically uninflamed or 'quiescent' mucosa from the right colon was examined in patients with proctosigmoiditis and between skip lesions in Crohn's disease patients. In the proctosigmoiditis group quiescent mucosa produced eicosanoids in similar quantities to control tissue. Coculture of quiescent plus inflamed tissue however, generated a marked increase in eicosanoid output in 12 of 20 of the patients and this was similar to the quantity obtained from two pieces of inflamed tissue. In the Crohn's disease group, quiescent mucosa produced more eicosanoids than control mucosa but production was markedly stimulated by coculture with inflamed mucosa in all patients. These findings suggest that in some patients with proctosigmoiditis and in all patients with Crohn's disease quiescent mucosa appears to be sensitised. A small but significant increase in the macrophage population may be partly responsible but it is likely that these and other cells are primed to release eicosanoids, and may be induced to do so by soluble mediators produced by actively inflamed tissue.