UC San Diego

Sepsis, a leading cause of mortality in hospitalized patients, is deeply impacted by sleep disruption, a common issue in hospital settings. The mechanisms connecting sleep disruption and sepsis outcomes remain elusive. We have demonstrated that sleep-disrupted C57BL/6 mice have a higher survival rate in an endotoxin-mediated peritonitis model. In this study, we test the hypothesis on whether the improved survival was due to impaired cell-intrinsic immune response to endotoxin. Using a tactile model for sleep disruption, we compared the ex vivo lipopolysaccharide (LPS) activation of primary peritoneal immune cells from sleep-disrupted mice to that of normal sleep control. After seven days of sleep disruption, cells from peritoneal lavage were plated and activated with LPS (100ng/mL) for 3 hours. We assessed inflammatory transcriptional activation by quantitative PCR (RT-qPCR) and found no reduction in cytokine genes such as Tnf⍺, Il-1ꞵ, Il-6, and Il-10 in sleep-disrupted mice. Flow cytometry of resident peritoneal macrophages showed that LPS induced STAT1 activation (phosphorylation at serine 727) was not reduced in peritoneal immune cells from sleep-disrupted mice compared to control. Finally, preliminary analysis of IL-1β secretion through ELISA also showed no sign of reduced immune activation after sleep disruption. Our findings suggest that the ex vivo activation of peritoneal immune cells by LPS is not dampened by sleep disruption. The mechanism for increased sepsis survival in sleep-disrupted mice lies outside of the initial contact between peritoneal immune cells and endotoxin, warranting further investigation to understand sleep-immune interactions during sepsis.