Cholecystokinin modulates mucosal immunoglobulin A function.
BACKGROUND
We have established that mucosal immunoglobulin A (IgA) production is highly dependent on cholecystokinin release and is markedly suppressed by glucocorticoids. The purpose of the present study was to examine the role of cholecystokinin on the functional responsiveness of the mucosal IgA system in glucocorticoid treated rats.


METHODS
A total of 24 Fischer rats were assigned to three groups of 8 animals each. 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 daily), a novel and potent long-acting cholecystokinin agonist (DEX+CCK). Animals were treated for 48 hours and killed. Duodenum was harvested, and the total mucosal concentration of cholecystokinin was measured by radioimmunoassay. Mucosal IgA was assayed by quantitation of immunoreactive cells in the ileum. Bacterial adherence was evaluated by quantitative culture of vigorously washed stripped cecal mucosa. Transepithelial electrical resistance, a measure of tight junction permeability, was assessed by mounting strips of adjacent cecal mucosa in Ussing chambers.


RESULTS
Glucocorticoid administration resulted in a statistically significant (p < 0.001) decrease in duodenal cholecystokinin, decreased IgA, and impaired mucosal immunity (increased bacterial adherence and decreased tissue resistance). Cholecystokinin administration preserved mucosal immune function in DEX-treated rats.


CONCLUSIONS
Cholecystokinin may play an important role in maintaining the functional responsiveness of mucosal immunity during catabolic stress.
Alverdy
J
J
Department of Surgery and Hematopathology, University of Chicago, IL 60637, USA.
Stern
E
E
Poticha
S
S
Baunoch
D
D
Adrian
T
T
D000818:Animals; D001422:Bacterial Adhesion; D002432:Cecum; D002766:Cholecystokinin / Q000819:agonists / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology; D004386:Duodenum; D005260:Female; D007082:Ileum; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D019108:Tight Junctions / Q000502:physiology
D007071:Immunoglobulin A, Secretory; D003907:Dexamethasone; D002766:Cholecystokinin