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The exact role of IL\u20106\u00a0in ARDS has proven difficult to study because it exhibits either pro\u2010 or anti\u2010inflammatory actions in mouse models of lung injury, depending on the model utilized. In order to improve understanding of the role of this complex cytokine in ARDS, we evaluated IL\u20106 using the clinically relevant combination of lipopolysaccharide (LPS) and ventilator\u2010induced lung injury (VILI) in<jats:italic>IL\u20106<jats:sup>\u2212\/\u2013<\/jats:sup><\/jats:italic>mice. Bronchoalveolar lavage fluid (BAL), whole\u2010lung tissue, and histology were evaluated for inflammatory markers of injury. Transendothelial electrical resistance was used to evaluate the action of IL\u20106 on endothelial cells in vitro. In wild\u2010type mice, the combination model showed a significant increase in lung injury compared to either LPS or VILI alone.<jats:italic>IL\u20106<jats:sup>\u2212\/\u2013<\/jats:sup><\/jats:italic>mice exhibited a statistically significant decrease in BAL cellular inflammation as well as lower histologic scores for lung injury, changes observed only in the combination model. A paradoxical increase in BAL total protein was observed in<jats:italic>IL\u20106<jats:sup>\u2212\/\u2013<\/jats:sup><\/jats:italic>mice exposed to LPS, suggesting that IL\u20106 provides protection from vascular leakage. However, in vitro data showed that IL\u20106, when combined with its soluble receptor, actually caused a significant increase in endothelial cell permeability, suggesting that the protection seen in vivo was likely due to complex interactions of IL\u20106 and other inflammatory mediators rather than to direct effects of IL\u20106. These studies suggest that a dual\u2010injury model exhibits utility in evaluating the pleiotropic effects of IL\u20106\u00a0in ARDS on inflammatory cells and lung endothelium.<\/jats:p>","DOI":"10.1086\/675991","type":"journal-article","created":{"date-parts":[[2014,4,28]],"date-time":"2014-04-28T21:18:32Z","timestamp":1398719912000},"page":"280-288","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":72,"title":["Pleiotropic Effects of Interleukin\u20106\u00a0in a \u201cTwo\u2010Hit\u201d Murine Model of Acute Respiratory Distress Syndrome"],"prefix":"10.1002","volume":"4","author":[{"given":"Julia L.","family":"Goldman","sequence":"first","affiliation":[{"name":"Institute of Personalized Respiratory Medicine University of Illinois at Chicago Chicago Illinois USA"},{"name":"Biological Resources Laboratory University of Illinois at Chicago Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saad","family":"Sammani","sequence":"additional","affiliation":[{"name":"Institute of Personalized Respiratory Medicine University of Illinois at Chicago Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie","family":"Kempf","sequence":"additional","affiliation":[{"name":"Institute of Personalized Respiratory Medicine University of Illinois at Chicago Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laleh","family":"Saadat","sequence":"additional","affiliation":[{"name":"Institute of Personalized Respiratory Medicine University of Illinois at Chicago Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleftheria","family":"Letsiou","sequence":"additional","affiliation":[{"name":"Institute of Personalized Respiratory Medicine University of Illinois at Chicago Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Personalized Respiratory Medicine University of Illinois at Chicago Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Moreno\u2010Vinasco","sequence":"additional","affiliation":[{"name":"Institute of Personalized Respiratory Medicine University of Illinois at Chicago Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia N.","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Institute of Personalized Respiratory Medicine University of Illinois at Chicago Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey D.","family":"Fortman","sequence":"additional","affiliation":[{"name":"Biological Resources Laboratory University of Illinois at Chicago Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe G. 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