Myocarditis and neutrophil-mediated vascular leakage but not cytokine storm associated with fatal murine leptospirosis.

Summary

Fatal murine leptospirosis was characterized by elevated IL-10, neutrophilia, and neutrophil-driven vascular leakage, with myocarditis as the principal cause of death. Contrary to assumptions from sepsis, a cytokine storm was not observed, reframing immunopathology and therapeutic targets.

Key Findings

• No cytokine storm or massive necroptosis; instead, elevated IL-10 and RANTES were detected.
• Severe disease associated with neutrophilia and neutrophil-mediated vascular permeability.
• Myocarditis was identified as the main cause of death in the murine model.

Clinical Implications

Clinicians should consider myocarditis in severe leptospirosis and the potential benefit of strategies that modulate neutrophil-driven vascular permeability, beyond anti-cytokine approaches.

Limitations

• Translation from murine intraperitoneal infection to human disease may be limited
• Sample sizes and detailed statistical parameters are not specified in the abstract

Future Directions

Validate myocarditis and neutrophil-targeted interventions in human leptospirosis and explore biomarkers predicting vascular leakage.