Combined Inhibition of C5 and CD14 Attenuates Systemic Inflammation in a Piglet Model of Meconium Aspiration Syndrome

Neonatology
Anub Mathew ThomasAndreas Barratt-Due

Abstract

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. To assess the efficacy of the combined inhibition of complement (C5) and CD14 on systemic inflammation induced in a forceful piglet MAS model. 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. 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 wa...Continue Reading

References

Aug 24, 2001·Pediatric Research·P A TølløfsrudO D Saugstad
Sep 7, 2004·Pediatric Research·Paal H H LindenskovTom E Mollnes
Jan 7, 2005·Pediatric Research·Paal H H LindenskovOla D Saugstad
Feb 4, 2005·Journal of Leukocyte Biology·Seymour J Klebanoff
Mar 25, 2005·Scandinavian Journal of Immunology·A CastellheimT E Mollnes
Feb 27, 2008·Pediatrics·Bodil SalvesenTom E Mollnes
Dec 17, 2008·Journal of Perinatology : Official Journal of the California Perinatal Association·J P Goldsmith
Sep 1, 2009·Proceedings of the National Academy of Sciences of the United States of America·Knut Tore LappegårdTom Eirik Mollnes
Jan 15, 2011·Mediators of Inflammation·Alex ZagariyaDharmapuri Vidyasagar
Sep 3, 2011·Immunological Reviews·Gabor L HorvathEicke Latz
Sep 26, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Corinna LauTom Eirik Mollnes
Feb 21, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Eivind O SamstadTerje Espevik
Feb 28, 2015·Neonatology·Paal Helge Haakonsen LindenskovTom Eirik Mollnes
Oct 24, 2015·Nature Reviews. Drug Discovery·B Paul Morgan, Claire L Harris
Dec 15, 2015·Pediatric Pulmonology·Nora HoferBernhard Resch

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Citations

Aug 16, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anub M ThomasAndreas Barratt-Due
Aug 19, 2021·ACS Chemical Biology·Alex MacphersonAlastair D G Lawson

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