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dc.contributor.authorHellerud, Bernt C
dc.contributor.authorOrrem, Hilde L.
dc.contributor.authorDybwik, Knut Gustav
dc.contributor.authorPischke, Søren Erik
dc.contributor.authorBarratt-Due, Andreas
dc.contributor.authorCastellheim, Albert
dc.contributor.authorFure, Hilde
dc.contributor.authorBergseth, Grete
dc.contributor.authorChristiansen, Dorte
dc.contributor.authorNunn, Miles A.
dc.contributor.authorEspevik, Terje
dc.contributor.authorLau, Corinna
dc.contributor.authorBrandtzæg, Petter
dc.contributor.authorNielsen, Erik Waage
dc.contributor.authorMollnes, Tom Eirik
dc.date.accessioned2018-03-19T11:07:14Z
dc.date.available2018-03-19T11:07:14Z
dc.date.issued2017-02-27
dc.description.abstractBackground<br> Fulminant meningococcal sepsis, characterized by overwhelming innate immune activation, mostly affects young people and causes high mortality. This study aimed to investigate the effect of targeting two key molecules of innate immunity, complement component C5, and co-receptor CD14 in the Toll-like receptor system, on the inflammatory response in meningococcal sepsis.<p> Methods<br> Meningococcal sepsis was simulated by continuous intravenous infusion of an escalating dose of heat-inactivated Neisseria meningitidis administered over 3 h. The piglets were randomized, blinded to the investigators, to a positive control group (n = 12) receiving saline and to an interventional group (n = 12) receiving a recombinant anti-CD14 monoclonal antibody together with the C5 inhibitor coversin.<p> Results<br> A substantial increase in plasma complement activation in the untreated group was completely abolished in the treatment group (p = 0.006). The following inflammatory mediators were substantially reduced in plasma in the treatment group: Interferon-γ by 75% (p = 0.0001), tumor necrosis factor by 50% (p = 0.01), Interleukin (IL)-8 by 50% (p = 0.03), IL-10 by 40% (p = 0.04), IL-12p40 by 50% (p = 0.03), and granulocyte CD11b (CR3) expression by 20% (p = 0.01).<p> Conclusion<br> Inhibition of C5 and CD14 may be beneficial in attenuating the detrimental effects of complement activation and modulating the cytokine storm in patients with fulminant meningococcal sepsis.en_US
dc.description.sponsorshipThe Research Council of Norwayen_US
dc.descriptionSource at <a href=https://doi.org/10.1186/s40560-017-0217-0> https://doi.org/10.1186/s40560-017-0217-0 </a>.en_US
dc.identifier.citationHellerud, B.C., Orrem, H.L., Dybwik, K., Pischke, S.E., Barratt-Due, A., Castellheim, A. ... Mollnes, T.E. (2017). Combined inhibition of C5 and CD14 efficiently attenuated the inflammatory response in a porcine model of meningococcal sepsis. Journal of Intensive Care, 5(21).en_US
dc.identifier.cristinIDFRIDAID 1515136
dc.identifier.doi10.1186/s40560-017-0217-0
dc.identifier.issn2052-0492
dc.identifier.urihttps://hdl.handle.net/10037/12372
dc.language.isoengen_US
dc.publisherBioMed Centralen_US
dc.relation.journalJournal of Intensive Care
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7-HEALTH/602699/EU/Disarming the intravascular innate immune response to improve treatment modalities for chronic kidney disease/DIREKT/en_US
dc.rights.accessRightsopenAccessen_US
dc.subjectEndotoxinen_US
dc.subjectChemokinesen_US
dc.subjectComplementen_US
dc.subjectCytokinesen_US
dc.subjectImmune responseen_US
dc.subjectNeisseria meningitidisen_US
dc.subjectSeptic shocken_US
dc.subjectToll-like receptoren_US
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750en_US
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750en_US
dc.titleCombined inhibition of C5 and CD14 efficiently attenuated the inflammatory response in a porcine model of meningococcal sepsisen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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