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dc.contributor.authorOrrem, Hilde Lang
dc.contributor.authorNilsson, Per
dc.contributor.authorPischke, Søren Erik
dc.contributor.authorKleveland, Ola
dc.contributor.authorYndestad, Arne
dc.contributor.authorEkholt, Karin
dc.contributor.authorDamås, Jan Kristian
dc.contributor.authorEspevik, Terje
dc.contributor.authorBendz, Bjørn
dc.contributor.authorHalvorsen, Bente
dc.contributor.authorGregersen, Ida
dc.contributor.authorWiseth, Rune
dc.contributor.authorAndersen, Geir Øystein
dc.contributor.authorUeland, Thor
dc.contributor.authorGullestad, Lars
dc.contributor.authorAukrust, Pål
dc.contributor.authorBarratt-Due, Andreas
dc.contributor.authorMollnes, Tom Eirik
dc.identifier.citationFrontiers in Immunology. 2018, 9:2035 1-11.nb_NO
dc.description.abstractBackground: Elevated interleukin-6 (IL-6) and complement activation are associated with detrimental effects of inflammation in coronary artery disease (CAD). The complement anaphylatoxins C5a and C3a interact with their receptors; the highly inflammatory C5aR1, and the C5aR2 and C3aR. We evaluated the effect of the IL-6 receptor (IL-6R)-antagonist tocilizumab on the expression of the anaphylatoxin receptors in whole blood from non-ST-elevation myocardial infarction (NSTEMI) patients. Separately, anaphylatoxin receptor expression in peripheral blood mononuclear cells (PBMC) from patients with different entities of CAD was investigated. Materials and Methods: NSTEMI patients were randomized to one dose of tocilizumab (n = 28) or placebo (n = 32) and observed for 6 months. Whole blood samples drawn at inclusion, at day 2, 3 and after 6 months were used for mRNA isolation. Plasma was prepared for analysis of complement activation measured as sC5b-9 by ELISA. Furthermore, patients with different CAD entities comprising stable angina pectoris (SAP, n = 22), non-ST-elevation acute coronary syndrome (NSTE-ACS, n = 21) and ST-elevation myocardial infarction (STEMI, n = 20) were included. PBMC was isolated from blood samples obtained at admission to hospital and mRNA isolated. Anaphylatoxin-receptor-expression was analyzed with qPCR using mRNA from whole blood and PBMC, respectively. Results: Our main findings were (i) Tocilizumab decreased C5aR1 and C5aR2 mRNA expression significantly (p < 0.001) and substantially (>50%) at day 2 and 3, whereas C3aR expression was unaffected. (ii) Tocilizumab did not affect complement activation. (iii) In analyzes of different CAD entities, C5aR1 expression was significantly increased in all CAD subgroups compared to controls with the highest level in the STEMI patients (p < 0.001). For C5aR2 and C3aR the expression compared to controls were more moderate with increased expression of C5aR2 in the STEMI group (p < 0.05) and C3aR in the NSTE-ACS group (p < 0.05). Conclusion: Expression of C5aR1 and C5aR2 in whole blood was significantly attenuated by IL-6R-inhibition in NSTEMI patients. These receptors were significantly upregulated in PBMC CAD patients with particularly high levels of C5aR1 in STEMI patients.nb_NO
dc.publisherFrontiers Medianb_NO
dc.rightsNavngivelse 4.0 Internasjonal*
dc.titleIL-6 receptor inhibition by tocilizumab attenuated expression of C5a receptor 1 and 2 in non-ST-elevation myocardial infarctionnb_NO
dc.title.alternativeIL-6 receptor inhibition by tocilizumab attenuated expression of C5a receptor 1 and 2 in non-ST-elevation myocardial infarctionnb_NO
dc.typeJournal articlenb_NO
dc.typePeer reviewednb_NO
dc.source.journalFrontiers in Immunologynb_NO
dc.description.localcodeCopyright © 2018 Orrem, Nilsson, Pischke, Kleveland, Yndestad, Ekholt, Damås, Espevik, Bendz, Halvorsen, Gregersen, Wiseth, Andersen, Ueland, Gullestad, Aukrust, Barratt-Due and Mollnes. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).nb_NO
cristin.unitnameInstitutt for sirkulasjon og bildediagnostikk
cristin.unitnameInstitutt for klinisk og molekylær medisin

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Navngivelse 4.0 Internasjonal
Except where otherwise noted, this item's license is described as Navngivelse 4.0 Internasjonal