Role of endogenous prostaglandins in preventing gastrointestinal ulceration: induction of ulcers by antibodies to prostaglandins

Abstract

Active immunization of rabbits with the principal, endogenous prostaglandins in the gastrointestinal mucosa induces gastrointestinal mucosal ulceration. Development of ulceration in prostaglandin-immunized rabbits appears to be a direct consequence of production of specific prostaglandin antibodies, as prostaglandin antibodies per se induce gastric ulceration within 9 days when administered intravenously to unimmunized rabbits. These studies suggest that endogenous prostaglandin E2, F2 alpha, D2, and I2 in the gastrointestinal tract play an important role in preventing mucosal ulceration. The mechanism of ulcer formation is not completely understood, but most evidence points toward prostaglandin antibodies inducing mucosal ulceration by binding to endogenous prostaglandins within the mucosa and thereby negating their mucosal protective effects. Gastric acid hypersecretion and complement fixation by prostaglandin-antiprostaglandin complexes are not likely involved in the development of mucosal ulceration in this model. Use of antibodies to interfere with prostaglandin action may be an alternative approach to investigate (a) the importance of endogenous prostaglandins in mediating mucosal protective mechanisms and (b) the role of prostaglandins in acute and chronic erosive/ulcerative diseases of the gastrointestinal tract.