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
International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Japan.
Department of Cardiology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
Elife. 2016 Dec 30;5:e21055. doi: 10.7554/eLife.21055.
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.
脓毒症是一种针对感染的全身性炎症反应，是重症监护病房中最常见的死亡原因。在此，我们报告，下丘脑神经肽食欲素经外周给药可提高脂多糖（LPS）诱导的内毒素休克小鼠的存活率，内毒素休克是一种经过充分研究的脓毒症休克模型。这一效应伴随着过度细胞因子产生的抑制以及儿茶酚胺和皮质酮的增加。我们发现，外周给予的食欲素在内毒素休克状态下可穿透血脑屏障，并且中枢给予食欲素也可抑制细胞因子产生并提高存活率，这表明食欲素在中枢神经系统（CNS）中有直接作用。食欲素有助于恢复LPS注射小鼠的体温并增强心血管功能。食欲素通过中枢神经系统对炎症反应的多效性调节可能构成脓毒症休克的一种新型治疗方法。
