Inhibition of acetylcholine induced intestinal motility by interleukin 1 beta in the rat.

BACKGROUND/AIMS The fact that raised interleukin 1 beta (IL 1 beta) concentrations have been found in the colonic mucosa of rats with experimentally induced colitis and of patients with inflammatory bowel disease indicates that this cytokine may participate in the disturbed intestinal motility seen during inflammatory bowel disease. This study investigated whether IL 1 beta could change the contractility of (a) a longitudinal muscle-myenteric plexus preparation from rat jejunum, ileum, and colon and (b) isolated jejunal smooth muscle cells. METHODS Isometric mechanical activity of intestinal segments was recorded using a force transducer. Moreover, smooth muscle cell length was measured by image analysis. RESULTS Although IL 1 beta did not affect jejunal, ileal, and colonic basal contractility, it significantly reduced contractile response to acetylcholine (ACh). This significant inhibition was seen only after 90 or 150 minutes of incubation with IL 1 beta. Pretreatment with cycloheximide blocked IL 1 beta induced inhibition of ACh stimulated jejunal contraction, suggesting that a newly synthesised protein was involved in the effect. NW-nitro-L-arginine (a nitric oxide synthase inhibitor) did not prevent the inhibition induced by IL 1 beta. Blocking neural transmission with tetrodotoxin abolished the IL 1 beta effect on jejunal contractile activity, whereas IL 1 beta had no effect on isolated and dispersed smooth muscle cells. CONCLUSIONS IL 1 beta inhibits ACh induced intestinal contraction and this inhibitory effect involves protein synthesis but is independent of nitric oxide synthesis. This effect does not involve a myogenic mechanism but is mediated through the myenteric plexus.