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

Background/Aims - The fact that raised interleukin 1β (IL1β) 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 IL1β 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 IL1β 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 IL1β. Pretreatment with cycloheximide blocked IL1β induced inhibition of ACh stimulated jejunal contraction, suggesting that a newly synthesised protein was involved in the effect. N"W-nitro-L-arginine (a nitric oxide synthase inhibitor) did not prevent the inhibition induced by IL1β. Blocking neural transmission with tetrodotoxin abolished the IL1β effect on jejunal contractile activity, whereas IL1β had no effect on isolated and dispersed smooth muscle cells. Conclusions - IL1β 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.