Abstract
Cytokines are involved in the symptoms of theacute phase response induced by infectious diseases inhumans as well as in animals, and interleukin-1β(IL-1 ) has a pivotal role in these changes. The role of central IL-1β in the gastrointestinalhypomotility and fever evoked by intravenousadministration of lipopolysaccharide (LPS) and themechanisms involved, were investigated in sheep as anexperimental model. LPS (0.1 μg/kg, intravenously)induced gastrointestinal hypomotility and fever thatwere significantly reduced by priorintracerebroventricular administration of IL-1βreceptor antagonist protein (IL-1ra, 2 μg/kg). The effects of LPS were mimickedby intracerebroventricular IL-1β (50 ng/kg),whereas IL-1β injected intravenously at the samedose only caused a slight and transient fever withoutmodifying the gastrointestinal motility. Priorintracerebroventricular administration of thecyclooxygenase inhibitor indomethacin (100 μg/kg) butnot the corticotropin-releasing factor (CRF) receptorantagonist α-helical CRF9-41 (5 μg/kg) blocked alleffects evoked by both LPS and IL-1β. These resultssuggest that in sheep, LPS induces digestive motordisturbances through a central release of IL-1β andprostaglandins.
Similar content being viewed by others
REFERENCES
Duranton A, Buéno L: Central opiate mechanism involved in gastro-intestinal motor disturbances induced by E. coli endotoxin in sheep. Life Sci 34:1795–1799, 1984
Pons L, Droy-Lefaix MT, Braquet P, Buéno L: Involvement of platelet-activating factor (PAF) in endotoxin-induced intestinal motor disturbances in rats. Life Sci 45:533–541, 1989
Fioramonti J, Buéno L, Du C: Alterations of digestive motility by Escherichia coli endotoxin in rabbits mediated through central opiate receptors. In Gastrointestinal Motility. C Roman (ed). Lancaster, MTP Press, 1984, pp 549–556
Dinarello CA: Interleukin-1 and interleukin-1 antagonism. Blood 77:1627–1652, 1991
Rothwell NJ: Functions and mechanisms of interleukin 1 in the brain. Trends Pharmacol Sci 12:430–436, 1991
Taché Y, Saperas E: Central actions of interleukin 1 on gastrointestinal function. Method Neurosci 17:169–184, 1993
Fargeas MJ, Fioramonti J, Buéno L: Central action of interleukin-1β on intestinal motility in rats: Mediation by two mechanisms. Gastroenterology 104:377–383, 1993
Kluger MJ: Fever: role of pyrogens and cryogens. Physiol Rev 71:93–127, 1991
Morimoto A, Murakami N, Nakamori T, Watanabe T: Ventromedial hypothalamus is highly sensitive to prostaglandin E2 for producing fever in rabbits. J Physiol 397:259–268, 1988
Komaki G, Arimura A, Koves K: Effect of intravenous injection of IL-1β on PGE2 levels in several brain areas as determined by microdialysis. Am J Physiol 262:E246–E251, 1992
Tilders FJH, DeRijk RH, van Dam A-M, Vincent VAM, Schotanus K, Persoons JHA: Activation of the hypothalamus-pituitary-adrenal axis by bacterial endotoxins: Routes and intermediate signals. Psychoneuroendocrinology 19:209–232, 1994
Berkenbosh F, van Oers J, Del Rey A, Tilders F, Besedovsky H: Corticotropin-releasing factor producing neurons in the rat activated by interleukin-1. Science 238:524–526, 1987
Cooper KE, Cranston WI, Honour AM: Observation on the site and mode of action of pyrogens in the rabbit brain. J Physiol 191:325–337, 1967
Rothwell NJ: CRF is involved in the pyrogenic and thermogenic effects of interleukin 1β in the rat. Am J Physiol 256:E111–E115, 1989
Ruckebusch Y, Buéno L: Electrical activity of the ovine jejunum and changes due to disturbances. Am J Dig Dis 20:1027–1035, 1975
Gregory PC, Rayner DV, Wenham G: Initiation of migrating myoelectric complex in sheep by duodenal acidification and hyperosmolarity: Role of vagus nerves. J Physiol 355:509–521, 1984
Harding R, Leek BF: The locations and activities of medullary neurones associated with ruminant forestomach motility. J Physiol 219:587–610, 1971
van Miert ASJPAM, van der Wal-Komproe LE, van Duin CTM: Effects of antipyretic agents on fever and ruminal stasis induced by endotoxins in conscious goats. Arch Int Pharmacodyn Ther 225:39–50, 1977
Ruckebusch Y: The electrical activity of the digestive tract of the sheep as an indication of the mechanical events in various regions. J Physiol 210:857–882, 1970
Buéno L, Sorraing JM, Fioramonti J: Influence of dopamine on rumino-reticular motility and rumination in sheep. J Vet Pharmacol Ther 6:93–98, 1983
Latour, A: Un dispositif simple d'analyse quantitative de l'electromyogramme intestinal chronique. Ann Rech Vet 4:347–353, 1973
van Miert ASJPAM, van Duin CTM, Wensing T: Fever and acute phase response induced in dwarf goats by endotoxin and bovine and human recombinant tumour necrosis factor alpha. J Vet Pharmacol Ther 15:332–342, 1992
De Saedeleer V, Wechsung E, Houvenaghel A: Endotoxin in the conscious piglet: Its effects on some general and gastrointestinal myoelectrical parameters. Vet Res Commun 15:227–238, 1991
van Miert ASJPAM, Kaya F, van Duin CTM: Changes in food intake and forestomach motility of dwarf goats by recombinant bovine cytokines (IL-1β, IL-2) and IFN-γ. Physiol Behav 52:859–864, 1992
van Duin CTM, Wensing T, van Miert ASJPAM: Acute phase responses induced in dwarf goats by r.BoIL-1β, r.BoIL-2 and r.BoIFNγ. Mediat Inflamm 1:201–206, 1992
Nakamori T, Morimoto A, Yamaguchi K, Watanabe T, Murakami N: Interleukin-1β production in the rabbit brain during endotoxin-induced fever. J Physiol 476:177–186, 1994
Hannum CH, Wilcox CJ, Arend WP, Joslin FG, Dripps DJ, Heimdahl PL, Armes LG, Sommer A, Eisenberg SP, Thompson RC: Interleukin-1 receptor antagonist activity of a human interleukin-1 inhibitor. Nature 343:336–340, 1990
Eisenberg SP, Evans JR, Arend WP, Verderber E, Brewer T, Hannum CH, Thompson RC: Primary structure and functional expression from a complementary DNA of a human interleukin-1 receptor antagonist. Nature 343:341–346, 1990
Licinio J, Wong M, Gold PW: Localization of interleukin-1 receptor antagonist mRNA in rat brain. Endocrinology 129:562–564, 1991
Opp MR, Krueger JM: Interleukin-1 receptor antagonist blocks interleukin-1-induced sleep and fever. Am J Physiol 260:R453–R457, 1991
Smith BK, Kluger MJ: Human IL-1 receptor antagonist partially suppresses LPS fever but not plasma levels of IL-6 in Fischer rats. Am J Physiol 263:R653–R655, 1992
Long NC, Otterness I, Kunkel SL, Vander AJ, Kluger MJ: The roles of interleukin-1β and tumor necrosis factor in lipopoly-saccharide fever in rats. Am J Physiol 259:R724–R728, 1990
Rothwell NJ, Busbridge NJ, Humphray H, Hissey P: Central actions of interleukin-1β on fever and thermogenesis. In The Physiological and Pathological Effects of Cytokines. CA Dinarello, MJ Kluger, MC Powanda, JJ Oppenheim (eds). New York, Wiley-Liss, 1990, pp 307–311
Klir JJ, McClellan JL, Kluger MJ: Interleukin-1β causes the increase in anterior hypothalamic interleukin-6 during LPS-induced fever in rats. Am J Physiol 266:R1845–R1848, 1994
Rothwell NJ: Mechanisms of the pyrogenic actions of cytokines. Eur Cytokine Netw 1:211–213, 1990
van Miert ASJPAM, van Duin CTM, Woutersen-van Nijnanten FM: Effects of intracerebroventricular injection of PGE2 and 5HT on body temperature, heart rate and rumen motility of conscious goats. Eur J Pharmacol 92:143–146, 1983
Gregory PC: Forestomach motility in the chronically vagotomized sheep. J Physiol 328:431–447, 1982
Malbert CH, Ruckebusch Y: Vagal influences on the phasic and tonic components of the motility of the ovine stomach and gastroduodenal area. J Gastrointest Motil 1:15–20, 1989
Ruckebusch Y: Gastrointestinal motor functions in ruminants. In Handbook of Physiology, The Gastrointestinal System, Sect 6, Vol I. SG Schultz, JD Wood, BB Rauner (eds). New York, Oxford University Press, 1989, pp 1225–1282
Rights and permissions
About this article
Cite this article
Plaza, M.A., Fioramonti, J. & Bueno, L. Role of Central Interleukin-1β in Gastrointestinal Motor Disturbances Induced by Lipopolysaccharide in Sheep. Dig Dis Sci 42, 242–250 (1997). https://doi.org/10.1023/A:1018837112572
Issue Date:
DOI: https://doi.org/10.1023/A:1018837112572