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. 1996 Sep;39(3):470–474. doi: 10.1136/gut.39.3.470

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

A C Aubé 1, H M Blottière 1, C Scarpignato 1, C Cherbut 1, C Rozé 1, J P Galmiche 1
PMCID: PMC1383358  PMID: 8949656

Abstract

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.

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Selected References

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  1. Beasley D., Cohen R. A., Levinsky N. G. Interleukin 1 inhibits contraction of vascular smooth muscle. J Clin Invest. 1989 Jan;83(1):331–335. doi: 10.1172/JCI113879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bitar K. N., Zfass A. M., Makhlouf G. M. Interaction of acetylcholine and cholecystokinin with dispersed smooth muscle cells. Am J Physiol. 1979 Aug;237(2):E172–E176. doi: 10.1152/ajpendo.1979.237.2.E172. [DOI] [PubMed] [Google Scholar]
  3. Bredt D. S., Hwang P. M., Snyder S. H. Localization of nitric oxide synthase indicating a neural role for nitric oxide. Nature. 1990 Oct 25;347(6295):768–770. doi: 10.1038/347768a0. [DOI] [PubMed] [Google Scholar]
  4. Cherbut C., Aubé A. C., Blottière H. M., Pacaud P., Scarpignato C., Galmiche J. P. In vitro contractile effects of short chain fatty acids in the rat terminal ileum. Gut. 1996 Jan;38(1):53–58. doi: 10.1136/gut.38.1.53. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dinarello C. A. Interleukin-1. Dig Dis Sci. 1988 Mar;33(3 Suppl):25S–35S. doi: 10.1007/BF01538128. [DOI] [PubMed] [Google Scholar]
  6. Fargeas M. J., Fioramonti J., Bueno L. Central action of interleukin 1 beta on intestinal motility in rats: mediation by two mechanisms. Gastroenterology. 1993 Feb;104(2):377–383. doi: 10.1016/0016-5085(93)90404-z. [DOI] [PubMed] [Google Scholar]
  7. Fleming I., Gray G. A., Julou-Schaeffer G., Parratt J. R., Stoclet J. C. Incubation with endotoxin activates the L-arginine pathway in vascular tissue. Biochem Biophys Res Commun. 1990 Sep 14;171(2):562–568. doi: 10.1016/0006-291x(90)91183-s. [DOI] [PubMed] [Google Scholar]
  8. Hurst S. M., Stanisz A. M., Sharkey K. A., Collins S. M. Interleukin 1 beta-induced increase in substance P in rat myenteric plexus. Gastroenterology. 1993 Dec;105(6):1754–1760. doi: 10.1016/0016-5085(93)91073-q. [DOI] [PubMed] [Google Scholar]
  9. Ikejima T., Okusawa S., Ghezzi P., van der Meer J. W., Dinarello C. A. Interleukin-1 induces tumor necrosis factor (TNF) in human peripheral blood mononuclear cells in vitro and a circulating TNF-like activity in rabbits. J Infect Dis. 1990 Jul;162(1):215–223. doi: 10.1093/infdis/162.1.215. [DOI] [PubMed] [Google Scholar]
  10. Khan I., Blennerhassett M. G., Kataeva G. V., Collins S. M. Interleukin 1 beta induces the expression of interleukin 6 in rat intestinal smooth muscle cells. Gastroenterology. 1995 Jun;108(6):1720–1728. doi: 10.1016/0016-5085(95)90133-7. [DOI] [PubMed] [Google Scholar]
  11. Knudsen M. A., Tøttrup A. A possible role of the L-arginine-nitric oxide pathway in the modulation of cholinergic transmission in the guinea-pig taenia coli. Br J Pharmacol. 1992 Nov;107(3):837–841. doi: 10.1111/j.1476-5381.1992.tb14533.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ligumsky M., Simon P. L., Karmeli F., Rachmilewitz D. Role of interleukin 1 in inflammatory bowel disease--enhanced production during active disease. Gut. 1990 Jun;31(6):686–689. doi: 10.1136/gut.31.6.686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Loppnow H., Libby P. Proliferating or interleukin 1-activated human vascular smooth muscle cells secrete copious interleukin 6. J Clin Invest. 1990 Mar;85(3):731–738. doi: 10.1172/JCI114498. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Mahida Y. R., Wu K., Jewell D. P. Enhanced production of interleukin 1-beta by mononuclear cells isolated from mucosa with active ulcerative colitis of Crohn's disease. Gut. 1989 Jun;30(6):835–838. doi: 10.1136/gut.30.6.835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Main C., Blennerhassett P., Collins S. M. Human recombinant interleukin 1 beta suppresses acetylcholine release from rat myenteric plexus. Gastroenterology. 1993 Jun;104(6):1648–1654. doi: 10.1016/0016-5085(93)90641-o. [DOI] [PubMed] [Google Scholar]
  16. Montuschi P., Tringali G., Currò D., Ciabattoni G., Parente L., Preziosi P., Navarra P. Evidence that interleukin-1 beta and tumor necrosis factor inhibit gastric fundus motility via the 5-lipoxygenase pathway. Eur J Pharmacol. 1994 Feb 11;252(3):253–260. doi: 10.1016/0014-2999(94)90170-8. [DOI] [PubMed] [Google Scholar]
  17. Morteau O., More J., Pons L., Bueno L. Platelet-activating factor and interleukin 1 are involved in colonic dysmotility in experimental colitis in rats. Gastroenterology. 1993 Jan;104(1):47–56. doi: 10.1016/0016-5085(93)90834-y. [DOI] [PubMed] [Google Scholar]
  18. Nakamura M., Saito H., Kasanuki J., Tamura Y., Yoshida S. Cytokine production in patients with inflammatory bowel disease. Gut. 1992 Jul;33(7):933–937. doi: 10.1136/gut.33.7.933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Palmer J. M., Koch T. R. Altered neuropeptide content and cholinergic enzymatic activity in the inflamed guinea pig jejunum during parasitism. Neuropeptides. 1995 May;28(5):287–297. doi: 10.1016/0143-4179(95)90045-4. [DOI] [PubMed] [Google Scholar]
  20. Sawada M., Hara N., Maeno T. Ionic mechanism of the outward current induced by extracellular ejection of interleukin-1 onto identified neurons of Aplysia. Brain Res. 1991 Apr 5;545(1-2):248–256. doi: 10.1016/0006-8993(91)91293-a. [DOI] [PubMed] [Google Scholar]
  21. Scarpignato C., Cartellá A., Zappia L. Effect of cimetropium bromide and other antispasmodic compounds on in vitro guinea-pig gallbladder. Methods Find Exp Clin Pharmacol. 1989 May;11(5):323–329. [PubMed] [Google Scholar]
  22. Shibata M., Blatteis C. M. Differential effects of cytokines on thermosensitive neurons in guinea pig preoptic area slices. Am J Physiol. 1991 Nov;261(5 Pt 2):R1096–R1103. doi: 10.1152/ajpregu.1991.261.5.R1096. [DOI] [PubMed] [Google Scholar]
  23. Sütö G., Király A., Taché Y. Interleukin 1 beta inhibits gastric emptying in rats: mediation through prostaglandin and corticotropin-releasing factor. Gastroenterology. 1994 Jun;106(6):1568–1575. doi: 10.1016/0016-5085(94)90412-x. [DOI] [PubMed] [Google Scholar]
  24. Tamaoki J., Yamawaki I., Takeyama K., Chiyotani A., Yamauchi F., Konno K. Interleukin-1 beta inhibits airway smooth muscle contraction via epithelium-dependent mechanism. Am J Respir Crit Care Med. 1994 Jan;149(1):134–137. doi: 10.1164/ajrccm.149.1.8111570. [DOI] [PubMed] [Google Scholar]
  25. Theodorou V., Eutamene H., Fioramonti J., Junien J. L., Bueno L. Interleukin 1 induces a neurally mediated colonic secretion in rats: involvement of mast cells and prostaglandins. Gastroenterology. 1994 Jun;106(6):1493–1500. doi: 10.1016/0016-5085(94)90402-2. [DOI] [PubMed] [Google Scholar]
  26. Vermillion D. L., Ernst P. B., Collins S. M. T-lymphocyte modulation of intestinal muscle function in the Trichinella-infected rat. Gastroenterology. 1991 Jul;101(1):31–38. doi: 10.1016/0016-5085(91)90456-u. [DOI] [PubMed] [Google Scholar]
  27. Vermillion D. L., Huizinga J. D., Riddell R. H., Collins S. M. Altered small intestinal smooth muscle function in Crohn's disease. Gastroenterology. 1993 Jun;104(6):1692–1699. doi: 10.1016/0016-5085(93)90647-u. [DOI] [PubMed] [Google Scholar]
  28. Wiklund C. U., Wiklund N. P., Gustafsson L. E. Modulation of neuroeffector transmission by endogenous nitric oxide: a role for acetylcholine receptor-activated nitric oxide formation, as indicated by measurements of nitric oxide/nitrite release. Eur J Pharmacol. 1993 Aug 24;240(2-3):235–242. doi: 10.1016/0014-2999(93)90904-v. [DOI] [PubMed] [Google Scholar]
  29. Woywodt A., Neustock P., Kruse A., Schwarting K., Ludwig D., Stange E. F., Kirchner H. Cytokine expression in intestinal mucosal biopsies. In situ hybridisation of the mRNA for interleukin-1 beta, interleukin-6 and tumour necrosis factor-alpha in inflammatory bowel disease. Eur Cytokine Netw. 1994 Jul-Aug;5(4):387–395. [PubMed] [Google Scholar]
  30. Xin L., Blatteis C. M. Blockade by interleukin-1 receptor antagonist of IL-1 beta-induced neuronal activity in guinea pig preoptic area slices. Brain Res. 1992 Jan 13;569(2):348–352. doi: 10.1016/0006-8993(92)90650-x. [DOI] [PubMed] [Google Scholar]

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