Diurnally-Regulated Corticosterone and Melatonin Inversely Control Endotoxin-Induced Acute Immune Responses.

Summary

In mice, afternoon LPS provoked stronger neutrophil-driven inflammation and higher mortality than midnight challenges. Cyclic corticosterone amplified hyperinflammation, whereas melatonin constrained it; septic patients exhibited high cortisol/low melatonin profiles mirroring these patterns, suggesting biomarker and chronobiological implications.

Key Findings

• Afternoon LPS challenge increased neutrophil activation, cytotoxic mediator release, and mortality versus midnight challenge.
• Corticosterone peaks associated with enhanced LPS-induced hyperinflammation; melatonin peaks restrained inflammatory magnitude.
• Septic patients showed high cortisol and low melatonin profiles paralleling murine patterns, suggesting a prognostic marker.

Clinical Implications

Cortisol and melatonin profiling could aid risk stratification; timing of interventions and potential melatonin adjuncts warrant evaluation to mitigate hyperinflammation in sepsis.

Limitations

• Human data are correlational; causality and optimal clinical intervention timing remain untested.
• LPS models may not fully recapitulate polymicrobial sepsis pathophysiology.

Future Directions

Prospective clinical validation of cortisol/melatonin as prognostic biomarkers and randomized trials of time-of-day–guided interventions or melatonin adjuncts in sepsis.