Peripherally administered orexin improves survival of mice with endotoxin shock
- University of Tsukuba, Japan
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.
Article and author information
Author details
Masashi Yanagisawa
Funding
Ministry of Education, Culture, Sports, Science, and Technology (WPI)
- Masashi Yanagisawa
Japan Society for the Promotion of Science (KAKENHI Grant Number 26220207)
- Masashi Yanagisawa
Japan Society for the Promotion of Science (FIRST Program)
- Masashi Yanagisawa
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Richard D Palmiter, Howard Hughes Medical Institute, University of Washington, United States
Ethics
Animal experimentation: Animal experiments were carried out in a humane manner after receiving approval from the Institutional Animal Care and Use Committee of the University of Tsukuba, and in accordance with the Regulation for Animal Experiments in our university and Fundamental Guideline for Proper Conduct of Animal Experiments and Related Activities in Academic Research Institutions under the jurisdiction of the Ministry of Education, Culture, Sports, Science and Technology (MEXT).Permit Nmber: 16-081
Version history
- Received: August 29, 2016
- Accepted: December 29, 2016
- Accepted Manuscript published: December 30, 2016 (version 1)
- Version of Record published: January 19, 2017 (version 2)
Copyright
© 2016, Ogawa et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Peripherally administered orexin improves survival of mice with endotoxin shock
eLife 5:e21055.
https://doi.org/10.7554/eLife.21055
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