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dc.contributor.authorThomas, Anub Mathew
dc.contributor.authorSchjalm, Camilla
dc.contributor.authorNilsson, Per
dc.contributor.authorLindenskov, Paal Helge H.
dc.contributor.authorRørtveit, Runa
dc.contributor.authorSolberg, Rønnaug
dc.contributor.authorSaugstad, Ola Didrik
dc.contributor.authorBerglund, Magnus M.
dc.contributor.authorStrömberg, Patrik
dc.contributor.authorLau, Corinna
dc.contributor.authorEspevik, Terje
dc.contributor.authorJansen, Johan Høgset
dc.contributor.authorCastellheim, Albert
dc.contributor.authorMollnes, Tom Eirik
dc.contributor.authorBarratt-Due, Andreas
dc.date.accessioned2018-09-05T11:15:06Z
dc.date.available2018-09-05T11:15:06Z
dc.date.issued2018-02-27
dc.description.abstract<p><i>Background</i>: Meconium aspiration syndrome (MAS) is a severe lung condition affecting newborns and it can lead to a systemic inflammatory response. We previously documented complement activation and cytokine release in a piglet MAS model. Additionally, we showed ex vivo that meconium-induced inflammation was dependent on complement and Toll-like receptors.</p> <p><i>Objectives</i>: To assess the efficacy of the combined inhibition of complement (C5) and CD14 on systemic inflammation induced in a forceful piglet MAS model.</p> <p><i>Methods</i>: Thirty piglets were randomly allocated to a treatment group receiving the C5-inhibitor SOBI002 and anti-CD14 (n = 15) and a nontreated control group (n = 15). MAS was induced by intratracheal meconium instillation, and the piglets were observed for 5 h. Complement, cytokines, and myeloperoxidase (MPO) were measured by ELISA.</p> <p><i>Results</i>: SOBI002 ablated C5 activity and the formation of the terminal complement complex in vivo. The combined inhibition attenuated the inflammasome cytokines IL-1β and IL-6 by 60 (p = 0.029) and 44% (p = 0.01), respectively, and also MPO activity in the bronchoalveolar fluid by 42% (p = 0.017). Ex vivo experiments in human blood revealed that the combined regimen attenuated meconium-induced MPO release by 64% (p = 0.008), but there was only a negligible effect with single inhibition, indicating a synergic cross-talk between the key molecules C5 and CD14.</p> <p><i>Conclusion</i>: Combined inhibition of C5 and CD14 attenuates meconium-induced inflammation in vivo and this could become a future therapeutic regimen for MAS.en_US
dc.descriptionSource at <a href=https://doi.org/10.1159/000486542> https://doi.org/10.1159/000486542</a>.en_US
dc.identifier.citationThomas, A.M., Schjalm, C., Nilsson, P., Lindenskov, P.H.H., Rørtveit, R., Solberg, R., ... Barratt-Due, A. (2018). Combined Inhibition of C5 and CD14 Attenuates Systemic Inflammation in a Piglet Model of Meconium Aspiration Syndrome. Neonatology, 113(4), 322-330. https://doi.org/10.1159/000486542en_US
dc.identifier.cristinIDFRIDAID 1592619
dc.identifier.doi10.1159/000486542
dc.identifier.issn1661-7800
dc.identifier.issn1661-7819
dc.identifier.urihttps://hdl.handle.net/10037/13668
dc.language.isoengen_US
dc.publisherKarger Publishersen_US
dc.relation.journalNeonatology
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750en_US
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750en_US
dc.subjectMeconium aspiration syndromeen_US
dc.subjectC5en_US
dc.subjectComplementen_US
dc.subjectCD14en_US
dc.subjectToll-like receptoren_US
dc.subjectInnate immunityen_US
dc.subjectSystemic inflammationen_US
dc.titleCombined Inhibition of C5 and CD14 Attenuates Systemic Inflammation in a Piglet Model of Meconium Aspiration Syndromeen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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