Intestinal lesions produced by prednisolone: prevention (cytoprotection) by 16,16-dimethyl prostaglandin E2.

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Abstract
Daily administration of prednisolone for 8 days to rats caused intestinal lesions consisting of multiple necrotic ulcers, often perforated, located on the antimesenteric side of the terminal ileum, and sometimes extending to the jejunum. These lesions were invariably infected (bacterial colonies were abundant histologically). Whether infection was secondary to the intestinal necrotic lesions is unknown. Because of their location, these prednisolone-induced intestinal lesions may serve as an experimental model for regional ileitis. 16,16-Dimethyl prostaglandin E2, given orally, inhibited the formation of these lesions, and the degree of inhibition was dose-dependent. A combination of 3 antibiotics (neomycin, bacitracin, polymyxin B) given orally also prevented the lesions. Although the pathogenesis of these intestinal lesions is unknown, the corticosteroid may deplete the intestine of endogenous prostaglandins by preventing the release of the prostaglandin precursor, arachidonic acid, from phospholipid stores. The cytoprotection afforded by administration of a prostaglandin appears therefore to be due to replacement therapy in an organ rendered deficient in endogenous prostaglandin(s). Prostaglandins may be necessary to maintain cellular integrity of the epithelium of the small intestine.