Peripherally administered orexin improves survival of mice with endotoxin shock

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

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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.

Original languageEnglish (US)
Article numbere21055
JournaleLife
Volume5
Issue numberDECEMBER2016
DOIs
StatePublished - Dec 30 2016

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ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Ogawa, Y., Irukayama-Tomobe, Y., Murakoshi, N., Kiyama, M., Ishikawa, Y., Hosokawa, N., Tominaga, H., Uchida, S., Kimura, S., Kanuka, M., Morita, M., Hamada, M., Takahashi, S., Hayashi, Y., & Yanagisawa, M. (2016). Peripherally administered orexin improves survival of mice with endotoxin shock. eLife, 5(DECEMBER2016), [e21055]. https://doi.org/10.7554/eLife.21055