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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.authorBarratt-Due, Andreas
dc.contributor.authorNielsen, Erik Waage
dc.contributor.authorMollnes, Tom Eirik
dc.date.accessioned2016-02-29T17:51:30Z
dc.date.available2016-02-29T17:51:30Z
dc.date.issued2015-11-27
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. <p>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. <p>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. <p>Conclusions: Combined inhibition of C5 and CD14 significantly improved survival, hemodynamic parameters and inflammation in a blinded, randomized trial of porcine polymicrobial sepsis.en_US
dc.descriptionLicense: Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)en_US
dc.identifier.citationCritical Care 2015, 19(415)en_US
dc.identifier.cristinIDFRIDAID 1339943
dc.identifier.doi10.1186/s13054-015-1129-9
dc.identifier.issn1466-609X
dc.identifier.urihttps://hdl.handle.net/10037/8587
dc.identifier.urnURN:NBN:no-uit_munin_8205
dc.language.isoengen_US
dc.publisherBioMed Centralen_US
dc.rights.accessRightsopenAccess
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750en_US
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750en_US
dc.titleCombined inhibition of complement and CD14 improved outcome in porcine polymicrobial sepsisen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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