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.
