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Since severe inflammation can be detrimental to the host, we investigated whether targeting the interleukin IL-1 pathway could reduce inflammation and tissue hypoxia, improving the outcome of IPA. The interplay between hypoxia and inflammation was investigated by <jats:italic>in vivo<\/jats:italic> imaging of hypoxia and measurement of cytokines in the lungs in a model of corticosteroid immunocompromised and in <jats:italic>Cxcr2<\/jats:italic> deficient mice. Severe hypoxia was observed following <jats:italic>Aspergillus<\/jats:italic> infection in both models and correlated with development of pulmonary inflammation and expression of hypoxia specific transcripts. Treatment with IL-1 receptor antagonist reduced hypoxia and slightly, but significantly reduced mortality in immunosuppressed mice, but was unable to reduce hypoxia in <jats:italic>Cxcr2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice. Our data provides evidence that the inflammatory response during invasive pulmonary aspergillosis and in particular the IL-1 axis, drives the development of hypoxia. Targeting the inflammatory IL-1 response could be used as a potential immunomodulatory therapy to improve the outcome of aspergillosis.<\/jats:p>","DOI":"10.1038\/srep26490","type":"journal-article","created":{"date-parts":[[2016,5,24]],"date-time":"2016-05-24T18:24:39Z","timestamp":1464114279000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Reducing hypoxia and inflammation during invasive pulmonary aspergillosis by targeting the Interleukin-1 receptor"],"prefix":"10.1038","volume":"6","author":[{"given":"Mark S.","family":"Gresnigt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdessalem","family":"Rekiki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orhan","family":"Rasid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Am\u00e9lie","family":"Savers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gr\u00e9gory","family":"Jouvion","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Dannaoui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Parlato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Fitting","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Brock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Marc","family":"Cavaillon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank L.","family":"van de Veerdonk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ouma\u00efma","family":"Ibrahim-Granet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,5,24]]},"reference":[{"key":"BFsrep26490_CR1","doi-asserted-by":"crossref","unstructured":"Brown, G. 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