APStracts 2:0103G, 1995.

Gastric antisecretory and anti-ulcer actions of interleukin-1 in rat involve different interleukin-1 receptor types. Mugridge, Kenneth G., Mauro Perretti, Paolo Ghiara, Cesira L. Galeotti, Marialuisa Melli, and Luca Parente. Istituto Ricerche Immunobiologiche Siena, Via Fiorentina,1., 53100 Siena, Italy

APStracts 2:0103G, 1995.

Limited knowledge exists concerning the IL-1 receptor type (IL-1Rt) mediating the potent antisecretory and gastroprotective actions of interleukin-1 (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 which preferentially binds to the IL-1RtII, and mutant yIL -1[beta]N7/Q, an analogue having equal affinity as IL-1[beta] for IL -1RtI and IL-1RtII, have been compared. Also, modulation of IL-1 gastric actions were investigated using monoclonal antibody (mAb) preparations raised against the 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 [mu]g/kg ip) reduced gastric acid secretion (50%, 79% and 78% respectively) indicating the importance of IL-1RtII binding for antisecretory activity. This was substantiated further in experiments using the mAb preparations which observed that IL-1[beta] (1 [mu]g/kg ip) antisecretory activity was reversed by mAbIL-1RtII (10-50 [mu]g/kg sc) but not by mAbIL-1RtI (50 [mu]g/kg sc). In contrast, at dosages ten-fold higher (10 [mu]g/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 paralled by decreased gastroprotective effect.

Received 31 October 1994; accepted in final form 18 May 1995.
APS Manuscript Number G437-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 May 1995.