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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\u2019s 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.<\/jats:p>","DOI":"10.7554\/elife.21055","type":"journal-article","created":{"date-parts":[[2016,12,30]],"date-time":"2016-12-30T08:00:16Z","timestamp":1483084816000},"source":"Crossref","is-referenced-by-count":48,"title":["Peripherally administered orexin improves survival of mice with endotoxin shock"],"prefix":"10.7554","volume":"5","author":[{"given":"Yasuhiro","family":"Ogawa","sequence":"first","affiliation":[{"name":"International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Irukayama-Tomobe","sequence":"additional","affiliation":[{"name":"International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, 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