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Combined Inhibition of C5 and CD14 Attenuates Systemic Inflammation in a Piglet Model of Meconium Aspiration Syndrome.
Oslo University Hospital, Rikshospitalet, Norway;University of Oslo, Norway.
Oslo University Hospital, Rikshospitalet, Norway;University of Oslo, Norway.
Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Oslo University Hospital, Rikshospitalet, Norway;University of Oslo, Norway. (Host response to Biomaterials)ORCID iD: 0000-0002-7192-5794
Oslo University Hospital, Norway.
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2018 (English)In: Neonatology, ISSN 1661-7800, E-ISSN 1661-7819, Vol. 113, no 4, p. 322-330Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: 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.

Place, publisher, year, edition, pages
S. Karger, 2018. Vol. 113, no 4, p. 322-330
Keywords [en]
C5, CD14, Complement, Innate immunity, Meconium aspiration syndrome, Systemic inflammation, Toll-like receptor
National Category
Respiratory Medicine and Allergy
Research subject
Natural Science, Medicine
Identifiers
URN: urn:nbn:se:lnu:diva-73332DOI: 10.1159/000486542ISI: 000433962200005PubMedID: 29486477OAI: oai:DiVA.org:lnu-73332DiVA, id: diva2:1200088
Available from: 2018-04-23 Created: 2018-04-23 Last updated: 2018-07-13Bibliographically approved

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