Show simple item record

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.identifier.citationNeonatology. 2018, 113 (4), 322-330.nb_NO
dc.description.abstractBackground: 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. Objectives: To assess the efficacy of the combined inhibition of complement (C5) and CD14 on systemic inflammation induced in a forceful piglet MAS model. Methods: 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. Results: 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. Conclusion: Combined inhibition of C5 and CD14 attenuates meconium-induced inflammation in vivo and this could become a future therapeutic regimen for MAS.nb_NO
dc.publisherKarger Publishersnb_NO
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internasjonal*
dc.titleCombined Inhibition of C5 and CD14 Attenuates Systemic Inflammation in a Piglet Model of Meconium Aspiration Syndromenb_NO
dc.typeJournal articlenb_NO
dc.typePeer reviewednb_NO
dc.description.localcode© 2018 The Author(s) Published by S. Karger AG, Basel. This article is licensed under the Creative Commons AttributionNonCommercial-NoDerivatives 4.0 International License (CC BYNC-ND) ( Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission.nb_NO
cristin.unitnameInstitutt for klinisk og molekylær medisin

Files in this item


This item appears in the following Collection(s)

Show simple item record

Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal