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Peripherally administered orexin improves survival of mice with endotoxin shock
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Peripherally administered orexin improves survival of mice with endotoxin shock
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Peripherally administered orexin improves survival of mice with endotoxin shock
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Journal Article
Peripherally administered orexin improves survival of mice with endotoxin shock
2016
Overview
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.
Publisher
eLife Sciences Publications, Ltd,eLife Science Publications, Ltd,eLife Sciences Publications Ltd
Subject
/ Blood-Brain Barrier - drug effects
/ Blood-Brain Barrier - immunology
/ Blood-Brain Barrier - metabolism
/ Body Temperature Regulation - drug effects
/ Body Temperature Regulation - immunology
/ Bradycardia - chemically induced
/ Brain
/ Chemokine CCL3 - antagonists & inhibitors
/ Chemokine CCL4 - antagonists & inhibitors
/ Humans
/ Interferon-gamma - antagonists & inhibitors
/ Interferon-gamma - immunology
/ Interleukin-17 - antagonists & inhibitors
/ Male
/ Mice
/ orexin
/ Orexins
/ Rodents
/ Sepsis
/ Shock, Septic - chemically induced
/ Shock, Septic - drug therapy
/ Spleen
/ Survival
/ Tumor Necrosis Factor-alpha - antagonists & inhibitors
/ Tumor Necrosis Factor-alpha - genetics
