title: Role of central interleukin-1 beta in gastrointestinal motor disturbances induced by lipopolysaccharide in sheep.
abstract: Cytokines are involved in the symptoms of the acute phase response induced by infectious diseases in humans as well as in animals, and interleukin-1 beta (IL-1 beta) has a pivotal role in these changes. The role of central IL-1 beta in the gastrointestinal hypomotility and fever evoked by intravenous administration of lipopolysaccharide (LPS) and the mechanisms involved, were investigated in sheep as an experimental model. LPS (0.1 microgram/kg, intravenously) induced gastrointestinal hypomotility and fever that were significantly reduced by prior intracerebroventricular administration of IL-1 receptor antagonist protein (IL-1ra, 2 micrograms/kg). The effects of LPS were mimicked by intracerebroventricular IL-1 beta (50 ng/kg), whereas IL-1 beta injected intravenously at the same dose only caused a slight and transient fever without modifying the gastrointestinal motility. Prior intracerebroventricular administration of the cyclooxygenase inhibitor indomethacin (100 micrograms/kg) but not the corticotropin-releasing factor (CRF) receptor antagonist alpha-helical CRF9-41 (5 micrograms/kg) blocked all effects by both LPS and IL-1 beta. These results suggest that in sheep, LPS induces digestive motor disturbances through a central release of IL-1 beta and prostaglandins.
authors.affiliation: Department of Pharmacology, INRA, Toulouse, France.
authors.forename: M A
authors.initials: MA
authors.lastname: Plaza
authors.forename: J
authors.initials: J
authors.lastname: Fioramonti
authors.forename: L
authors.initials: L
authors.lastname: Bueno
mesh_terms: D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D004926:Escherichia coli; D005260:Female; D005334:Fever / Q000139:chemically induced; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D006727:Hormone Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology; D007276:Injections, Intraventricular; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D012756:Sheep; D012795:Sialoglycoproteins / Q000494:pharmacology
chemical_list: D016861:Cyclooxygenase Inhibitors; D006727:Hormone Antagonists; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D008070:Lipopolysaccharides; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; C069206:alpha helical corticotropin-releasing hormone; D003346:Corticotropin-Releasing Hormone; D007213:Indomethacin