Gastric antisecretory and anti-ulcer actions of IL-1 in rat involve different IL-1 receptor types.
Limited knowledge exists concerning the interleukin-1 (IL-1) receptor type (IL-1RT) mediating the potent antisecretory and gastro-protective actions of IL-1. In the present study, the gastric actions of IL-1 beta and two related mutant proteins, yIL-1 beta delta 4, an analogue that preferentially binds to IL-1-RTII, and mutant yIL-1 beta N7/Q, an analogue that has equal affinity as IL-1 beta for IL-1RTI and IL-1RTII, have been compared. Modulation of IL-1 gastric actions were also investigated using monoclonal antibody (MAb) preparations raised against IL-1RTI or IL-1RTII. In the pylorus-ligated rat, yIL-1 beta delta 4, yIL-1 beta N7/Q, and IL-1 beta (all at 1 microgram/kg ip) reduced gastric acid secretion (50, 79, and 78%, respectively), indicating the importance of IL-1RTII binding for antisecretory activity. This was further substantiated in experiments using the MAb preparations, which showed that IL-1 beta (1 microgram/kg ip) antisecretory activity was reversed by MAb IL-1RTII (10-50 micrograms/kg sc) but not by MAb IL-1RTI (50 micrograms/kg sc). In contrast, at dosages 10-fold higher (10 micrograms/kg ip) than that used in the study to inhibit acid secretion, IL-1 beta and yIL-1N7/Q equally reduced (approximately 80%) indomethacin-induced gastric damage, but yIL-1 beta delta 4 was ineffective. The results using yIL-1 beta delta 4 indicated that impairment of IL-1RTI binding capacity appeared to be paralleled by a decreased gastroprotective effect.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D005753:Gastric Mucosa / Q000378:metabolism*; D007213:Indomethacin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D017472:Receptors, Interleukin-1 / Q000276:immunology / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013270:Stomach / Q000187:drug effects
D000897:Anti-Ulcer Agents; D000911:Antibodies, Monoclonal; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D007213:Indomethacin