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Lung injury is a known risk factor for the development of posttraumatic complications, but information on the long-term course of the pulmonary inflammatory response and treatment with mild hypothermia are scarce.<\/jats:p><\/jats:sec><jats:sec id=\"sec002\"><jats:title>Aim<\/jats:title><jats:p>To investigate the pulmonary inflammatory response to multiple trauma and hemorrhagic shock in a porcine model of combined trauma and to assess the immunomodulatory properties of mild hypothermia.<\/jats:p><\/jats:sec><jats:sec id=\"sec003\"><jats:title>Methods<\/jats:title><jats:p>Following induction of trauma (blunt chest trauma, liver laceration, tibia fracture), two degrees of hemorrhagic shock (45 and 50%) over 90 (n = 30) and 120 min. (n = 20) were induced. Animals were randomized to hypothermia (33\u00b0C) or normothermia (38\u00b0C). We evaluated bronchoalveolar lavage (BAL) fluid and tissue levels of cytokines and investigated changes in microRNA- and gene-expression as well as tissue apoptosis.<\/jats:p><\/jats:sec><jats:sec id=\"sec004\"><jats:title>Results<\/jats:title><jats:p>We observed a significant induction of Interleukin (IL) 1\u03b2, IL-6, IL-8, and Cyclooxygenase-2 mRNA in lung tissue. Likewise, an increased IL-6 protein concentration could be detected in BAL-fluid, with a slight decrease of IL-6 protein in animals treated with hypothermia. Lower IL-10 protein levels in normothermia and higher IL-10 protein concentrations in hypothermia accompanied this trend. Tissue apoptosis increased after trauma. However, intervention with hypothermia did not result in a meaningful reduction of pro-inflammatory biomarkers or tissue apoptosis.<\/jats:p><\/jats:sec><jats:sec id=\"sec005\"><jats:title>Conclusion<\/jats:title><jats:p>We observed signs of a time-dependent pulmonary inflammation and apoptosis at the site of severe trauma, and to a lower extent in the trauma-distant lung. Intervention with mild hypothermia had no considerable effect during 48 hours following trauma.<\/jats:p><\/jats:sec>","DOI":"10.1371\/journal.pone.0278766","type":"journal-article","created":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T18:40:20Z","timestamp":1670438420000},"page":"e0278766","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Pulmonary inflammatory response and immunomodulation to multiple trauma and hemorrhagic shock in pigs"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9641-3691","authenticated-orcid":true,"given":"Marc-Alexander","family":"Oestreich","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Seidel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilhelm","family":"Bertrams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Helge","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0607-4644","authenticated-orcid":true,"given":"Martin","family":"Sassen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorsten","family":"Steinfeldt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hinnerk","family":"Wulf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2767-3606","authenticated-orcid":true,"given":"Bernd","family":"Schmeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,12,7]]},"reference":[{"key":"pone.0278766.ref001","author":"WHO","year":"2008","journal-title":"The 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Bauer","year":"1991","journal-title":"Stat Med"},{"issue":"1","key":"pone.0278766.ref033","doi-asserted-by":"crossref","DOI":"10.1186\/s13017-017-0154-1","article-title":"Thoracic trauma severity contributes to differences in intensive care therapy and mortality of severely injured patients: analysis based on the TraumaRegister DGU\u00ae.","volume":"12","author":"J Bayer","year":"2017","journal-title":"World J Emerg Surg."},{"issue":"3","key":"pone.0278766.ref034","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s00068-002-1192-1","article-title":"Diagnostics and Scoring in Blunt Chest Trauma.","volume":"28","author":"F Hildebrand","year":"2002","journal-title":"European Journal of Trauma"},{"issue":"2","key":"pone.0278766.ref035","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1097\/SHK.0000000000000279","article-title":"Potential biomarker panel for predicting organ dysfunction and acute coagulopathy in a polytrauma porcine model","volume":"43","author":"YC 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mice: Distinct early response compared with single trauma or \u201cdouble-hit\u201d injury.","volume":"74","author":"S Weckbach","year":"2013","journal-title":"Journal of Trauma and Acute Care Surgery"},{"issue":"3","key":"pone.0278766.ref043","first-page":"951","article-title":"Caspase 3 expression and plasma level of Fas ligand as apoptosis biomarkers in inflammatory endotoxemic lung injury","volume":"57","author":"R Fodor","year":"2016","journal-title":"Rom J Morphol Embryol"},{"issue":"3","key":"pone.0278766.ref044","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.prp.2009.12.002","article-title":"The role of apoptosis in the pathophysiology of Acute Respiratory Distress Syndrome (ARDS): an up-to-date cell-specific review.","volume":"206","author":"V Galani","year":"2010","journal-title":"Pathol Res Pract."},{"issue":"4","key":"pone.0278766.ref045","doi-asserted-by":"crossref","first-page":"2217","DOI":"10.4049\/jimmunol.163.4.2217","article-title":"Soluble Fas ligand induces epithelial cell apoptosis in humans with acute lung injury (ARDS).","volume":"163","author":"G Matute-Bello","year":"1999","journal-title":"J Immunol"},{"key":"pone.0278766.ref046","doi-asserted-by":"crossref","first-page":"762840","DOI":"10.1155\/2012\/762840","article-title":"Facts and fiction: the impact of hypothermia on molecular mechanisms following major challenge.","volume":"2012","author":"M Frink","year":"2012","journal-title":"Mediators Inflamm."},{"issue":"1","key":"pone.0278766.ref047","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1097\/00004647-200201000-00003","article-title":"Mild Hypothermia Reduces Apoptosis of Mouse Neurons In vitro Early in the Cascade","volume":"22","author":"L Xu","year":"2002","journal-title":"J Cereb Blood Flow Metab"},{"issue":"5","key":"pone.0278766.ref048","first-page":"1084","article-title":"Alterations in gene expression after induction of profound hypothermia for the treatment of lethal hemorrhage","volume":"68","author":"HB Alam","year":"2010","journal-title":"J Trauma"},{"issue":"5","key":"pone.0278766.ref049","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.cyto.2005.06.008","article-title":"Effects of hypothermia and re-warming on the inflammatory response in a murine multiple hit model of trauma","volume":"31","author":"F Hildebrand","year":"2005","journal-title":"Cytokine"},{"issue":"3","key":"pone.0278766.ref050","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1097\/TA.0000000000000545","article-title":"Evolving beyond the vicious triad: Differential mediation of traumatic coagulopathy by injury, shock, and resuscitation.","volume":"78","author":"ME Kutcher","year":"2015","journal-title":"Journal of Trauma and Acute Care Surgery."},{"issue":"1","key":"pone.0278766.ref051","doi-asserted-by":"crossref","DOI":"10.1038\/s41572-021-00264-3","article-title":"Trauma-induced coagulopathy.","volume":"7","author":"EE Moore","year":"2021","journal-title":"Nature Reviews Disease Primers"},{"issue":"16","key":"pone.0278766.ref052","doi-asserted-by":"crossref","first-page":"8719","DOI":"10.3390\/ijerph18168719","article-title":"Hypothermia in Trauma.","volume":"18","author":"MJ Van Veelen","year":"2021","journal-title":"Int J Environ Res Public Health"},{"issue":"1","key":"pone.0278766.ref053","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.injury.2011.10.013","article-title":"Effects of accidental hypothermia on posttraumatic complications and outcome in multiple trauma patients.","volume":"44","author":"P Mommsen","year":"2013","journal-title":"Injury"},{"key":"pone.0278766.ref054","article-title":"Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation.","author":"J Arrich","year":"2016","journal-title":"Cochrane Database of Systematic 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