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dc.contributor.authorSkjeflo, Espen Waage
dc.contributor.authorSagatun, Caroline
dc.contributor.authorDybwik, Knut
dc.contributor.authorAam, Sturla
dc.contributor.authorUrving, Sven Haakon
dc.contributor.authorNunn, Miles A.
dc.contributor.authorFure, Hilde
dc.contributor.authorLau, Corinna
dc.contributor.authorBrekke, Ole Lars
dc.contributor.authorHuber-Lang, Markus
dc.contributor.authorEspevik, Terje
dc.contributor.authorBarratt-Due, Andreas
dc.contributor.authorNielsen, Erik Waage
dc.contributor.authorMollnes, Tom Eirik
dc.date.accessioned2016-02-26T11:45:54Z
dc.date.accessioned2016-03-18T12:46:31Z
dc.date.available2016-02-26T11:45:54Z
dc.date.available2016-03-18T12:46:31Z
dc.date.issued2015
dc.identifier.citationCritical Care 2015, 19(415)nb_NO
dc.identifier.issn1466-609X
dc.identifier.urihttp://hdl.handle.net/11250/2382496
dc.description.abstractIntroduction Sepsis is an exaggerated and dysfunctional immune response to infection. Activation of innate immunity recognition systems including complement and the Toll-like receptor family initiate this disproportionate inflammatory response. The aim of this study was to explore the effect of combined inhibition of the complement component C5 and the Toll-like receptor co-factor CD14 on survival, hemodynamic parameters and systemic inflammation including complement activation in a clinically relevant porcine model of polymicrobial sepsis. Methods Norwegian landrace piglets (4 ± 0.5 kg) were blindly randomized to a treatment group (n = 12) receiving the C5 inhibitor coversin (OmCI) and anti-CD14 or to a positive control group (n = 12) receiving saline. Under anesthesia, sepsis was induced by a 2 cm cecal incision and the piglets were monitored in standard intensive care for 8 hours. Three sham piglets had a laparotomy without cecal incision or treatment. Complement activation was measured as sC5b-9 using enzyme immunoassay. Cytokines were measured with multiplex technology. Results Combined C5 and CD14 inhibition significantly improved survival (p = 0.03). Nine piglets survived in the treatment group and four in the control group. The treatment group had significantly lower pulmonary artery pressure (p = 0.04) and ratio of pulmonary artery pressure to systemic artery pressure (p < 0.001). Plasma sC5b-9 levels were significantly lower in the treatment group (p < 0.001) and correlated significantly with mortality (p = 0.006). IL-8 and IL-10 were significantly (p < 0.05) lower in the treatment group. Conclusions Combined inhibition of C5 and CD14 significantly improved survival, hemodynamic parameters and inflammation in a blinded, randomized trial of porcine polymicrobial sepsis.nb_NO
dc.language.isoengnb_NO
dc.publisherBioMed Centralnb_NO
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleCombined inhibition of complement and CD14 improved outcome in porcine polymicrobial sepsisnb_NO
dc.typePeer reviewednb_NO
dc.typeJournal articleen_GB
dc.date.updated2016-02-26T11:45:54Z
dc.rights.holder© Skjeflo et al. 2015nb_NO
dc.source.volume19:415nb_NO
dc.source.journalCritical Carenb_NO
dc.identifier.doi10.1186/s13054-015-1129-9
dc.identifier.cristin1339943
dc.description.localcode© 2015 Skjeflo et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.nb_NO


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