Modulatory effects of exogenous estradiol during endotoxemia

Area of Science:

• Immunology
• Endocrinology
• Metabolomics

Background:

• Lipopolysaccharide (LPS)-induced endotoxemia is a critical model for studying systemic inflammation.
• Biological sex and hormonal status significantly influence inflammatory and metabolic responses.
• Estradiol's role in modulating immune responses during sepsis remains incompletely understood.

Purpose of the Study:

• To investigate the impact of exogenous estradiol on inflammatory, metabolic, and organ-function responses to LPS-induced endotoxemia in a murine model.
• To compare responses between male, female, and estradiol-supplemented female mice.
• To identify sex- and hormone-dependent variations in physiological and molecular changes during endotoxemia.

Main Methods:

• Murine model of LPS-induced endotoxemia.
• Administration of LPS to male, female, and estradiol-supplemented female mice.
• Monitoring of systemic physiological parameters (blood pressure, GFR, blood gases, temperature) over 6 hours.
• Post-mortem analysis of inflammatory markers, organ injury biomarkers, and plasma metabolomics.

Main Results:

• Estradiol supplementation attenuated early hepatic and cardiac injury markers.
• Reduced cardiac nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) expression was observed in estradiol-supplemented mice.
• Organ- and endpoint-dependent effects were noted, with renal differences emerging later.
• Metabolite profiles showed changes consistent with altered metabolic and redox responses.

Conclusions:

• Elevated estradiol levels modulate early inflammatory and metabolic responses during endotoxemia.
• Estradiol does not provide uniform protection across all organs or sexes.
• Biological sex and hormonal status are crucial variables in endotoxemia models.
• Findings generate hypotheses for future research on hormone-dependent immune-metabolic regulation.