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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.identifier.citationCritical Care 2015, 19(415)nb_NO
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.publisherBioMed Centralnb_NO
dc.titleCombined inhibition of complement and CD14 improved outcome in porcine polymicrobial sepsisnb_NO
dc.typePeer reviewednb_NO
dc.typeJournal articleen_GB
dc.rights.holder© Skjeflo et al. 2015nb_NO
dc.source.journalCritical Carenb_NO
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 (, 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 ( applies to the data made available in this article, unless otherwise stated.nb_NO

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