Orexin Receptor Antagonism Improves Sleep Quality and Mitigates Lipopolysaccharide-Induced Inflammatory Responses in a Mouse Model.

ABSTRACT: Alterations in the immune system, stemming from sleep/wakefulness disorders, increase the risk of inflammatory pathologies. Orexin, a hypothalamic neuropeptide, regulates sleep and wakefulness. However, the role of orexin in inflammatory responses-whether it is protective or pathological-is still unclear. In this study, our aim was to elucidate the role of orexin in sleep and inflammatory states through the examination of a lipopolysaccharide (LPS)-induced systemic inflammatory model and the effects of daridorexant, a dual orexin receptor antagonist. Intraperitoneal LPS administration significantly decreased rapid eye-movement (REM) sleep and wakefulness while increasing non-REM sleep. Pretreatment with daridorexant enhanced REM sleep recovery in LPS-induced systemic inflammation, evidence

SUBMITTER: Horiuchi D 

PROVIDER: S-EPMC12785484 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature