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In mice, we found that lipopolysaccharide (LPS) and high-volume ventilation, LPS-HVV, lead to hypoxemia with neutrophil extracellular traps (NETs) formation in the alveoli. Furthermore,\n                    <jats:italic>\n                      Il1r1\n                      <jats:sup>-\/-<\/jats:sup>\n                    <\/jats:italic>\n                    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\u00b0C body temperature) prevented hypoxemia development, reducing albumin leakage, IL-1\u03b2, gasdermin D (GSDMD), and NETs formation. We also observed that LPS-primed macrophages, when stimulated at 32\u00b0C with ATP or nigericin, release less IL-1\u03b2 associated with reduced GSDMD cleavage. Thus, hypothermia is an important modulating factor in the NLRP3 inflammasome activation, IL-1\u03b2 release, and NETs formation, preventing LPS-HVV-induced acute respiratory failure.\n                  <\/jats:p>","DOI":"10.7554\/elife.101990","type":"journal-article","created":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T08:25:06Z","timestamp":1740990306000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.101990","source":"Crossref","is-referenced-by-count":2,"title":["Hypothermia protects against ventilator-induced lung injury by limiting IL-1\u03b2 release and NETs formation"],"prefix":"10.7554","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7722-0701","authenticated-orcid":true,"given":"Nobuyuki","family":"Nosaka","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02pammg90","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pediatrics, Division of Infectious Diseases and Immunology, Guerin Children\u2019s at Cedars-Sinai 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