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IL-1 Receptor Antagonist Blocks the Lipopolysaccharide-Induced Inhibition of Gastric Motility in Freely Moving Conscious Rats

โœ Scribed by Yoshihiro Tsuchiya, Tsukasa Nozu, Shima Kumei, Masumi Ohhira, Toshikatsu Okumura


Book ID
118298806
Publisher
Springer US
Year
2012
Tongue
English
Weight
436 KB
Volume
57
Category
Article
ISSN
0163-2116

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โœฆ Synopsis


Background and Aims

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 0.2ย mg/kg or more significantly inhibited MI. The inhibition started immediately after the administration of LPS and lasted over 1ย h. Intraperitoneal injection of IL-1ฮฒ potently decreased MI while neither IL-6 nor TNF-ฮฑ inhibited gastric motility, suggesting IL-1ฮฒ 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 20ย mg/kg significantly blocked the inhibition of gastric contractility by LPS at a dose of 0.2ย mg/kg.

Conclusions

These results suggest for the first time that LPS or IL-1ฮฒ 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.


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