INTERLEUKIN-1 RECEPTOR ANTAGONIST DOES NOT PREVENT ENDOTOXIN-INDUCED INHIBITION OF GASTRIC-ACID SECRETION IN RATS

The underlying mechanisms involved in endotoxin-induced inhibition of gastric acid secretion were investigated in conscious rats with pylorus ligation for 2 hr. Intraperitoneal injection of endotoxin (0.1, 1, and 5 mu g/rat) inhibited gastric acid output by 31%, 80%, and 84% respectively. Intraperitoneal endotoxin (1 mu g/rat) -induced inhibition of gastric acid secretion was not altered by pretreatment with the interleukin-1 receptor antagonist IL-IRA, indomethacin, naloxone, or capsaicin. Treatments were injected peripherally at doses previously shown to antagonize the antisecretory effect of exogenous interlertkin-1 beta, to inhibit prostaglandin synthesis in the stomach and brain, to block opiate receptors, and to alter functioning of unmyelinated afferent nerve fibers. These results indicate that the antisecretory effect of endotoxin can be expressed by factors other than interleukin-1, prostaglandins, or opioid peptides that do not require the integrity of capsaicin-sensitive afferent pathways.