CHOLECYSTOKININ MODULATES MUCOSAL IMMUNOGLOBULIN-A FUNCTION

Background. We have established that mucosal immunoglobulin A (IgA) pr oduction is highly dependent on cholecystokinin release and is markedl y suppressed by glucocorticoids. The purpose of the present study was to examine the role of cholecystokinin on the functional responsivenes s of the mucosal IgA system in glucocorticoid treated rats. Methods. A total of 24 Fischer rats were assigned to three groups of 8 animals e ach. Animals were injected with vehicle (CON), dexamethasone (DEX) (0. 08 mg/150 g), or DEX (0.08 mg/150 gm) and ARL1294KF (500 ng twice dail y), a novel and potent lon acting cholecystokinin agonist (DEX+CCK). A nimals were treated for 48 hours and killed. Duodenum was harvested an d the total mucosal concentration of cholecystokinin was measured by r adioimmunoassay. Mucosal IgA was assayed by quantitation of immunoreac tive cells in the ileum. Bacterial adherence was evaluated by quantita tive culture of vigorously washed stripped cecal mucosa. Transepitheli al electrical resistance, a measure of tight junction permeability, wa s assessed by mounting strips of adjacent cecal mucosa in Ussing chamb ers. Results. Glucocorticoid administration resulted in a statisticall y significant (P < 0.001) decrease in duodenal cholecystokinin, decrea sed IgA, and impaired mucosal immunity (increased bacterial adherence and decreased tissue resistance). Cholecystokinin administration prese rved mucosal immune function in DEX-treated rats. Conclusions. Cholecy stokinin may play an important role in maintaining functional responsi veness of mucosal immunity during catabolic stress.