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We investigated the impact of splenectomy on immune responses in the 1<jats:sup>st<\/jats:sup>-hit polytrauma alone and on survival in the post-traumatic sepsis (2<jats:sup>nd<\/jats:sup> hit). Female BALB\/c mice underwent polytrauma (1<jats:sup>st<\/jats:sup> hit) consisting of either a) TH: femur fracture, hemorrhagic shock or b) TSH: splenectomy, femur fracture, hemorrhagic shock. Additionally, the polytrauma hit was followed by cecal ligation and puncture (CLP) 48\u2009h later and compared to CLP alone. Splenectomy improved the 28-day survival in secondary sepsis to 92%\u00a0(from 62%), while TH lowered it to 46% (p\u2009&lt;\u20090.05). The improved survival was concurrent with lower release of inflammatory cytokines (IL-6, CXCL-1, MCP-1) and increase of C5a post-CLP. In the polytrauma hit alone, TSH induced stronger neutrophilia (1.9 fold) and lymphocytosis (1.7 fold) when compared to TH mice. Moreover, TSH resulted in a 41% rise of regulatory T-cells and reduced the median fluorescence intensity of MHC-2 on monocytes by 55% within 48\u2009h (p\u2009&lt;\u20090.05). Conversely, leukocyte phagocytic capacity was significantly increased by 4-fold after TSH despite a similar M1\/M2 macrophage profile in both groups. Summarizing, splenectomy provoked both immuno-suppressive and immuno-stimulatory responses but was life-saving in secondary sepsis. Additionally, the polytrauma components in 2-hit models should be tested for their effects on outcome; the presumed end-effect of the 1<jats:sup>st<\/jats:sup> hit solely based on the common immuno-inflammatory parameters could be misleading.<\/jats:p>","DOI":"10.1038\/s41598-018-33232-1","type":"journal-article","created":{"date-parts":[[2018,10,1]],"date-time":"2018-10-01T15:14:10Z","timestamp":1538406850000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Splenectomy modulates early immuno-inflammatory responses to trauma-hemorrhage and protects mice against secondary sepsis"],"prefix":"10.1038","volume":"8","author":[{"given":"S.","family":"Drechsler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Zipperle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Rademann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Jafarmadar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Klotz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Bahrami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1321-9883","authenticated-orcid":false,"given":"M. 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