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bioRxiv · 10.1101/2024.09.02.610778

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

Nosaka, N.·Borges, V.·Martinon, D.·Crother, T. R.·Arditi, M.·Shimada, K.
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Abstract

Although mechanical ventilation is a critical intervention for acute respiratory distress syndrome (ARDS), it can trigger an IL-1{beta}-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, Il1r1-/- 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 {degrees}C body temperature) prevented hypoxemia development, reducing albumin leakage, IL-1{beta}, gasdermin D (GSDMD) and NETs formation. We also observed that LPS-primed macrophages, when stimulated at 32{degrees}C with ATP or nigericin, release less IL-1{beta} associated with reduced GSDMD cleavage. Thus, hypothermia is an important modulating factor in the NLRP3 inflammasome activation, IL-1{beta} release and NETs formation, preventing LPS-HVV-induced acute respiratory failure.

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Nosaka, N., Borges, V., Martinon, D., Crother, T. R., Arditi, M., Shimada, K.. 2024-09-03. Hypothermia protects against ventilator-induced lung injury by limiting IL-1beta release and NETs formation. https://doi.org/10.1101/2024.09.02.610778

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