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

Research output: Contribution to journalArticle

8 Citations (Scopus)

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

Fingerprint

Neurology
Septic Shock
Endotoxins
Lipopolysaccharides
Shock
Central Nervous System
Cytokines
Intensive care units
Corticosterone
Neuropeptides
Body Temperature
Blood-Brain Barrier
Catecholamines
Intensive Care Units
Cause of Death
Sepsis
Modulation
Infection
Temperature
Therapeutics

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., ... Yanagisawa, M. (2016). Peripherally administered orexin improves survival of mice with endotoxin shock. eLife, 5(DECEMBER2016), [e21055]. https://doi.org/10.7554/eLife.21055

Peripherally administered orexin improves survival of mice with endotoxin shock. / Ogawa, Yasuhiro; Irukayama-Tomobe, Yoko; Murakoshi, Nobuyuki; Kiyama, Maiko; Ishikawa, Yui; Hosokawa, Naoto; Tominaga, Hiromu; Uchida, Shuntaro; Kimura, Saki; Kanuka, Mika; Morita, Miho; Hamada, Michito; Takahashi, Satoru; Hayashi, Yu; Yanagisawa, Masashi.

In: eLife, Vol. 5, No. DECEMBER2016, e21055, 30.12.2016.

Research output: Contribution to journalArticle

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, vol. 5, no. DECEMBER2016, e21055. https://doi.org/10.7554/eLife.21055
Ogawa Y, Irukayama-Tomobe Y, Murakoshi N, Kiyama M, Ishikawa Y, Hosokawa N et al. Peripherally administered orexin improves survival of mice with endotoxin shock. eLife. 2016 Dec 30;5(DECEMBER2016). e21055. https://doi.org/10.7554/eLife.21055
Ogawa, Yasuhiro ; Irukayama-Tomobe, Yoko ; Murakoshi, Nobuyuki ; Kiyama, Maiko ; Ishikawa, Yui ; Hosokawa, Naoto ; Tominaga, Hiromu ; Uchida, Shuntaro ; Kimura, Saki ; Kanuka, Mika ; Morita, Miho ; Hamada, Michito ; Takahashi, Satoru ; Hayashi, Yu ; Yanagisawa, Masashi. / Peripherally administered orexin improves survival of mice with endotoxin shock. In: eLife. 2016 ; Vol. 5, No. DECEMBER2016.
@article{fea4015c01f54a2b8a8c9cfa8af2f5f4,
title = "Peripherally administered orexin improves survival of mice with endotoxin shock",
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.",
author = "Yasuhiro Ogawa and Yoko Irukayama-Tomobe and Nobuyuki Murakoshi and Maiko Kiyama and Yui Ishikawa and Naoto Hosokawa and Hiromu Tominaga and Shuntaro Uchida and Saki Kimura and Mika Kanuka and Miho Morita and Michito Hamada and Satoru Takahashi and Yu Hayashi and Masashi Yanagisawa",
year = "2016",
month = "12",
day = "30",
doi = "10.7554/eLife.21055",
language = "English (US)",
volume = "5",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
number = "DECEMBER2016",

}

TY - JOUR

T1 - Peripherally administered orexin improves survival of mice with endotoxin shock

AU - Ogawa, Yasuhiro

AU - Irukayama-Tomobe, Yoko

AU - Murakoshi, Nobuyuki

AU - Kiyama, Maiko

AU - Ishikawa, Yui

AU - Hosokawa, Naoto

AU - Tominaga, Hiromu

AU - Uchida, Shuntaro

AU - Kimura, Saki

AU - Kanuka, Mika

AU - Morita, Miho

AU - Hamada, Michito

AU - Takahashi, Satoru

AU - Hayashi, Yu

AU - Yanagisawa, Masashi

PY - 2016/12/30

Y1 - 2016/12/30

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85010672879&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85010672879&partnerID=8YFLogxK

U2 - 10.7554/eLife.21055

DO - 10.7554/eLife.21055

M3 - Article

C2 - 28035899

AN - SCOPUS:85010672879

VL - 5

JO - eLife

JF - eLife

SN - 2050-084X

IS - DECEMBER2016

M1 - e21055

ER -