dc.contributor.author | Hellerud, Bernt C | |
dc.contributor.author | Orrem, Hilde L. | |
dc.contributor.author | Dybwik, Knut Gustav | |
dc.contributor.author | Pischke, Søren Erik | |
dc.contributor.author | Barratt-Due, Andreas | |
dc.contributor.author | Castellheim, Albert | |
dc.contributor.author | Fure, Hilde | |
dc.contributor.author | Bergseth, Grete | |
dc.contributor.author | Christiansen, Dorte | |
dc.contributor.author | Nunn, Miles A. | |
dc.contributor.author | Espevik, Terje | |
dc.contributor.author | Lau, Corinna | |
dc.contributor.author | Brandtzæg, Petter | |
dc.contributor.author | Nielsen, Erik Waage | |
dc.contributor.author | Mollnes, Tom Eirik | |
dc.date.accessioned | 2017-11-22T14:56:18Z | |
dc.date.available | 2017-11-22T14:56:18Z | |
dc.date.created | 2017-11-17T09:59:29Z | |
dc.date.issued | 2017 | |
dc.identifier.citation | Journal of Intensive Care. 2017, 5:21 1-9. | nb_NO |
dc.identifier.issn | 2052-0492 | |
dc.identifier.uri | http://hdl.handle.net/11250/2467631 | |
dc.description.abstract | Background
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.
Methods
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.
Results
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).
Conclusion
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. | nb_NO |
dc.language.iso | eng | nb_NO |
dc.publisher | BioMed Central | nb_NO |
dc.rights | Navngivelse 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/deed.no | * |
dc.title | Combined inhibition of C5 and CD14 efficiently attenuated the inflammatory response in a porcine model of meningococcal sepsis | nb_NO |
dc.type | Journal article | nb_NO |
dc.type | Peer reviewed | nb_NO |
dc.description.version | publishedVersion | nb_NO |
dc.source.pagenumber | 1-9 | nb_NO |
dc.source.volume | 5:21 | nb_NO |
dc.source.journal | Journal of Intensive Care | nb_NO |
dc.identifier.doi | 10.1186/s40560-017-0217-0 | |
dc.identifier.cristin | 1515136 | |
dc.description.localcode | © The Author(s). 2017 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 |
cristin.unitcode | 194,65,15,0 | |
cristin.unitname | Institutt for klinisk og molekylær medisin | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |