Inhibition of antigen-induced secretion in the rat jejunum by interferon alpha/beta.
Intestine from rats sensitized to egg albumin (EA) antigen responds to EA challenge with an increase in short-circuit current (Isc), indicative of predominantly chloride secretion. Here, we have examined the role of interferon alpha/beta (IFN alpha/beta) in the control of this event. Muscle-stripped jejunal segments from sensitized rats, mounted in Ussing chambers, displayed a reduced response to EA-challenge in the presence of IFN alpha/beta (100-1000 U/ml), when the cytokine was incubated with the tissue for > or = 60 min; serosal and luminal responses were significantly reduced by ca.32-47% and ca.50-80%, respectively. Preabsorption with an anti-IFN alpha/beta antibody abolished this inhibition. IFN alpha/beta did not influence the secretory response of the tissues to histamine, serotonin, bethanechol, or forskolin, suggesting that IFN alpha/beta does not affect the epithelium directly. IFN alpha/beta had no effect on Isc changes induced by electrical transmural stimulation of mucosal nerves in the tissue, nor did neuronal blockade with tetrodotoxin influence the action of IFN alpha/beta. These data indicate that the effect of IFN alpha/beta is not neuronally mediated. The normal anti-secretory actions of diphenhydramine (H1-antagonist) and piroxicam (cylooxygenase inhibitor) upon antigen-activation of mast cells, were not apparent in the presence of IFN alpha/beta. This suggests that IFN alpha/beta inhibits intestinal hypersensitivity by acting directly on mast cells. This hypothesis was confirmed by inhibition of antigen-induced release of the specific mucosal mast cell marker, rat mast cell protease II, in tissues treated with IFN alpha/beta. These findings suggest that IFN alpha/beta can function as an intestinal anti-inflammatory agent by stabilizing mucosal mast cells.
McKay
D M
DM
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Bienenstock
J
J
Perdue
M H
MH
D000818:Animals; D000941:Antigens; D002712:Chlorides / Q000378:metabolism; D006969:Hypersensitivity, Immediate / Q000503:physiopathology; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology; D007370:Interferon Type I / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology*; D007583:Jejunum / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins
D000941:Antigens; D002712:Chlorides; D007370:Interferon Type I; D011994:Recombinant Proteins; D016899:Interferon-beta; D010047:Ovalbumin