Opposing Effects of the Circadian Timing on Acute and Chronic Phases of Sepsis

Apr 14, 2026FASEB journal : official publication of the Federation of American Societies for Experimental Biology

Opposite Effects of Body Clock Timing on Early and Late Stages of Sepsis

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Abstract

Mice injected with lipopolysaccharide during their active phase (ZT18) showed a more intense inflammatory response but higher long-term survival rates compared to those injected during their rest phase (ZT6).

  • The acute inflammatory response was more severe in mice during the active phase, with increased hypothermia and elevated levels of tumor necrosis factor (TNF-α) within 24 hours.
  • Higher acute-phase mortality was observed in the active phase (ZT18) group compared to the rest phase (ZT6) group.
  • By day 5, the ZT18 group demonstrated a higher survival rate despite their initial severe response.
  • The long-term survival advantage in the ZT18 group was linked to stronger metabolic resilience and quicker recovery of energy expenditure.
  • Lesioning the central clock eliminated the differences in mortality and metabolic responses, suggesting the central clock regulates these effects.

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