Peripherally Administered Orexin Improves Survival of Mice with Endotoxin Shock

Overview

Journal Elife

Specialty Biology

Date 2016 Dec 31

PMID 28035899

Citations 21

Authors

Yasuhiro Ogawa

Yoko Irukayama-Tomobe

Nobuyuki Murakoshi

Maiko Kiyama

Yui Ishikawa

Naoto Hosokawa

Hiromu Tominaga

Shuntaro Uchida

Saki Kimura

Mika Kanuka

Miho Morita

Michito Hamada

Satoru Takahashi

Yu Hayashi

Masashi Yanagisawa

Affiliations

Soon will be listed here.

Abstract

Sepsis is a systemic inflammatory response to infection, accounting for the most common cause of death in intensive care units. Here, we report that peripheral administration of the hypothalamic neuropeptide orexin improves the survival of mice with lipopolysaccharide (LPS) induced endotoxin shock, a well-studied septic shock model. The effect is accompanied by a suppression of excessive cytokine production and an increase of catecholamines and corticosterone. We found that peripherally administered orexin penetrates the blood-brain barrier under endotoxin shock, and that central administration of orexin also suppresses the cytokine production and improves the survival, indicating orexin's direct action in the central nervous system (CNS). Orexin helps restore body temperature and potentiates cardiovascular function in LPS-injected mice. Pleiotropic modulation of inflammatory response by orexin through the CNS may constitute a novel therapeutic approach for septic shock.

Citing Articles

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Blais A, Lan A, Blachier F, Benamouzig R, Jouet P, Couvineau A Int J Mol Sci. 2023; 24(11).

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Ghrelin prevents lethality in a rat endotoxemic model through central effects on the vagal pathway and adenosine A2B signaling : Brain ghrelin and anti-septic action.

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