Hypothermia protects against ventilator-induced lung injury by limiting IL-1β release and NETs formation.

Apr 16, 2025bioRxiv : the preprint server for biology

Cooling the body may help prevent lung damage from ventilators by reducing IL-1β release and the formation of NETs.

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Abstract

Therapeutic hypothermia at 32 °C prevented hypoxemia in a mouse model of ventilator-induced lung injury.

Mechanical ventilation can cause ventilator-induced lung injury linked to IL-1β complications.
In mice, high-volume ventilation combined with LPS resulted in hypoxemia and increased formation of neutrophil extracellular traps (NETs) in the lungs.
Mice treated with therapeutic hypothermia showed no hypoxemia and reduced NET formation.
Therapeutic hypothermia decreased levels of inflammatory markers including albumin leakage, IL-1β, and gasdermin D.
At lower temperatures, LPS-primed macrophages released less IL-1β when stimulated, indicating a potential mechanism for reduced inflammation.

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Although mechanical ventilation is a critical intervention for acute respiratory distress syndrome (ARDS), it can trigger an IL-1β-associated complication known as ventilator-induced lung injury. In mice, we found that LPS and high-volume ventilation, LPS-HVV, leads to hypoxemia with neutrophil extracellular traps (NETs) formation in the alveoli. Furthermore,LPS-HVV mice did not develop hypoxemia and had reduced NETs, indicating that IL-1R1 signaling is important for NETs formation and hypoxemia. Therapeutic hypothermia (TH) is known to reduce the release of inflammatory mediators. In LPS-HVV mice, TH (32 °C body temperature) prevented hypoxemia development, reducing albumin leakage, IL-1β, gasdermin D (GSDMD) and NETs formation. We also observed that LPS-primed macrophages, when stimulated at 32°C with ATP or nigericin, release less IL-1β associated with reduced GSDMD cleavage. Thus, hypothermia is an important modulating factor in the NLRP3 inflammasome activation, IL-1β release and NETs formation, preventing LPS-HVV-induced acute respiratory failure. Il1r1 -/-

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