{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:39:29Z","timestamp":1790811569515,"version":"4.1.0"},"reference-count":22,"publisher":"S. Karger AG","issue":"4","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neonatology"],"published-print":{"date-parts":[[2018]]},"abstract":"<b><i>Background:<\/i><\/b> 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. <b><i>Objectives:<\/i><\/b> To assess the efficacy of the combined inhibition of complement (C5) and CD14 on systemic inflammation induced in a forceful piglet MAS model. <b><i>Methods:<\/i><\/b> Thirty piglets were randomly allocated to a treatment group receiving the C5-inhibitor SOBI002 and anti-CD14 (<i>n<\/i> = 15) and a nontreated control group (<i>n<\/i> = 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. <b><i>Results:<\/i><\/b> SOBI002 ablated C5 activity and the formation of the terminal complement complex in vivo<i>.<\/i> The combined inhibition attenuated the inflammasome cytokines IL-1\u03b2 and IL-6 by 60 (<i>p<\/i> = 0.029) and 44% (<i>p<\/i> = 0.01), respectively, and also MPO activity in the bronchoalveolar fluid by 42% (<i>p<\/i> = 0.017). Ex vivo experiments<i><\/i> 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. <b><i>Conclusion:<\/i><\/b> Combined inhibition of C5 and CD14 attenuates meconium-induced inflammation in vivo and this could become a future therapeutic regimen for MAS.<\/jats:p>","DOI":"10.1159\/000486542","type":"journal-article","created":{"date-parts":[[2018,2,27]],"date-time":"2018-02-27T22:01:24Z","timestamp":1519768884000},"page":"322-330","source":"Crossref","is-referenced-by-count":10,"title":["Combined Inhibition of C5 and CD14 Attenuates Systemic Inflammation in a Piglet Model of Meconium Aspiration Syndrome"],"prefix":"10.1159","volume":"113","author":[{"given":"Anub\u00a0Mathew","family":"Thomas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Schjalm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per\u00a0H.","family":"Nilsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paal\u00a0H.H.","family":"Lindenskov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runa","family":"R\u00f8rtveit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00f8nnaug","family":"Solberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3166-5254","authenticated-orcid":false,"given":"Ola\u00a0Didrik","family":"Saugstad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus\u00a0M.","family":"Berglund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrik","family":"Str\u00f6mberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinna","family":"Lau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terje","family":"Espevik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan\u00a0H\u00f8gset","family":"Jansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Castellheim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom\u00a0Eirik","family":"Mollnes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Barratt-Due","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2018,2,27]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1159\/000369373"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1038\/jp.2008.156"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1203\/01.PDR.0000082017.97479.39"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1155\/2010\/204831"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.2005.01532.x"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.23349"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1203\/01.PDR.0000141983.32466.2A"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2007-0878"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2009.12.015"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.3VMR0316-132R"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-200109000-00020"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4657"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1301653"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1203\/01.PDR.0000153870.66197.D1"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2013.05.221"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.1985.tb01871.x"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1204697"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2007-1697"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2011.01050.x"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1302484"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0903613106"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1177\/1753425913482993"}],"container-title":["Neonatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/486542","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/486542","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T16:34:35Z","timestamp":1745426075000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000486542"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018]]},"references-count":22,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2018,5,31]]},"published-print":{"date-parts":[[2018,5,29]]}},"URL":"https:\/\/doi.org\/10.1159\/000486542","archive":["Portico"],"relation":{},"ISSN":["1661-7800","1661-7819"],"issn-type":[{"value":"1661-7800","type":"print"},{"value"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