Abdominal surgery-induced inhibition of gastric emptying is mediated in part by interleukin-1 beta.

Abstract

The role of interleukin-1 beta (IL-1 beta) in abdominal surgery-induced inhibition of gastric emptying was investigated. Abdominal surgery was performed under halothane anesthesia, and 5 min later, the 20-min rate of gastric emptying was measured by the phenol red method in conscious animals. In nonoperated animals, intravenous IL-1 beta dose dependently decreased gastric emptying from 55.1 +/- 1.7% in controls to 8.0 +/- 3.5% (P < 0.05) after treatment with 1 microgram IL-1 beta. Prior administration of IL-1 beta receptor antagonist (IL-1 beta ra; 200 micrograms) completely abolished the inhibitory effects of IL-1 beta. Surgery inhibited gastric emptying by 83.4% compared with rats receiving anesthesia alone. IL-1 beta ra (200 micrograms) reversed the inhibition of gastric emptying by 34.8% (P < 0.05) in the early (30 min) postoperative period and by 32.3% (P < 0.05) in the late (120 min) postoperative period. Use of calcitonin gene-related peptide-(8-37) [CGRP-(8-37)] in combination with IL-1 beta ra in operated animals resulted in no further reversal in the inhibition of gastric emptying: CGRP-(8-37)-treated animals = 42.1 +/- 4.1%; CGRP-(8-37) + IL-1 beta ra = 38.0 +/- 4.4% (not significant). Moreover, in nonoperated animals, CGRP-(8-37) completely abolished the effects of intravenous IL-1 beta on gastric emptying: IL-1 beta-treated animals = 11.1 +/- 2.0%; IL-1 beta + CGRP-(8-37) = 40.6 +/- 6.4% (P < 0.05). These results suggest that IL-1 beta is mediating part of the gastric ileus observed after abdominal surgery through the release of CGRP from the visceral afferents.