title: IL-1 receptor antagonist blocks the lipopolysaccharide-induced inhibition of gastric motility in freely moving conscious rats.
abstract: OBJECTIVE
  Endotoxin/lipopolysaccharide (LPS) alters gastrointestinal functions. However, little is known as to whether LPS could change gastric antral contractility in freely moving conscious animals. We tried to clarify this problem and the associated mechanisms.
  
  
  METHODS
  In this study, we recorded intraluminal gastric pressure waves in freely moving conscious rats by manometric catheter located in the antrum. Area under the manometric trace was evaluated as motor index (MI).
  
  
  RESULTS
  Intraperitoneal injection of LPS at doses of 0.2 mg/kg or more significantly inhibited MI. The inhibition started immediately after the administration of LPS and lasted over 1 h. Intraperitoneal injection of IL-1β potently decreased MI while neither IL-6 nor TNF-α inhibited gastric motility, suggesting IL-1β specifically reduced gastric motility. Next, we examined the hypothesis that endogenous IL-1 mediates the LPS-induced inhibition of gastric motility. To address the speculation, an IL-1 receptor antagonist (IL-1Ra) was used to block IL-1 signaling. Pretreatment with IL-1Ra at a dose of 20 mg/kg significantly blocked the inhibition of gastric contractility by LPS at a dose of 0.2 mg/kg.
  
  
  CONCLUSIONS
  These results suggest for the first time that LPS or IL-1β is capable of inhibiting gastric motility in conscious rats and that endogenously released IL-1 may mediate the LPS-evoked inhibition of gastric antral motility. This evidence also led us to speculate that IL-1Ra may be a therapeutic tool for patients with disturbed gastrointestinal functions under septic conditions.
authors.affiliation: Department of General Medicine, Asahikawa Medical University, Midorigaoka Higashi 2-1-1, Asahikawa 078-8510, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Tsuchiya
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Nozu
authors.forename: Shima
authors.initials: S
authors.lastname: Kumei
authors.forename: Masumi
authors.initials: M
authors.lastname: Ohhira
authors.forename: Toshikatsu
authors.initials: T
authors.lastname: Okumura
mesh_terms: D000818:Animals; D003243:Consciousness; D004305:Dose-Response Relationship, Drug; D005769:Gastrointestinal Motility / Q000187:drug effects*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D017472:Receptors, Interleukin-1; D014409:Tumor Necrosis Factor-alpha