%0 Journal Article
%A Huse, Camilla
%A Murphy, Sarah Louise
%A Yang, Kuan
%A Balzer, Nora Reka
%A Stokke, Mathis K
%A Anstensrud, Anne Kristine
%A Bjerkeli, Vigdis
%A Rentz, Thiago
%A Jha, Prabhash Kumar
%A Ugland, Hege Katrin
%A Michelsen, Annika E
%A Ueland, Thor
%A Holm, Sverre
%A Tøllefsen, Ingvild Maria
%A Bendz, Bjørn
%A Kleveland, Ola
%A Andersen, Geir Øystein
%A Gullestad, Lars
%A Louch, William E
%A Woxholt, Sindre
%A Osnes, Liv
%A Broch, Kaspar
%A Ulas, Thomas
%A Aukrust, Pål
%A Libby, Peter
%A Halvorsen, Bente
%A Dahl, Tuva B
%T The effects of interleukin-6-receptor inhibition on monocytes in STEMI: a substudy of the ASSAIL-MI trial.
%J EBioMedicine
%V 121
%@ 2352-3964
%C Amsterdam [u.a.]
%I Elsevier
%M DZNE-2025-01262
%P 105960
%D 2025
%X Interleukin-6 receptor (IL-6R) inhibition by tocilizumab improves myocardial salvage index (MSI) in ST-elevation myocardial infarction (STEMI). However, the mechanisms for this effect remain unclear.This pre-defined exploratory sub-study of the ASSAIL-MI trial enumerated circulating monocytes and examined their transcriptome profile in relation to the MSI and peak troponin T (TnT) in STEMI patients randomiseded to tocilizumab (n = 101) or placebo (n = 98). RNA sequencing was performed on peripheral monocytes in 14 patients. To elaborate the in vivo findings, in vitro chemotaxis and apoptosis assays were performed on THP-1 monocytes and cardiomyocyte (HL-1) cell lines, respectively.STEMI patients had increased monocyte counts at 24 h and 3-7 days after hospitalisation/PCI and this increase was attenuated by tocilizumab. Lower monocyte levels at 24 h were associated with lower TnT levels and higher MSI. Monocyte gene expression suggested that tocilizumab modulated cytokine signalling pathways related to myocardial remodelling, apoptosis, and chemotaxis, potentially through a decrease in suppressor of cytokine signalling 3 (SOCS3). In vitro, tocilizumab limited apoptosis of cardiomyocytes exposed to ischemia/reperfusion and reduced chemotaxis in monocytes exposed to IL-6.These findings suggest that IL-6R inhibition by tocilizumab during STEMI is associated with reduced monocyte counts and cardioprotective alterations in monocyte signalling potentially linked to the downregulation of SOCS3.This work was supported by the South-Eastern Norway Regional Health Authority (no. 2019067) and The Research Council of Norway (no. 282867) The ASSAIL-MI main study was supported by an independent grant from ROCHE who also provided drugs/placebo for infusion.
%K Humans
%K Monocytes: metabolism
%K Monocytes: drug effects
%K ST Elevation Myocardial Infarction: drug therapy
%K ST Elevation Myocardial Infarction: metabolism
%K ST Elevation Myocardial Infarction: blood
%K Male
%K Receptors, Interleukin-6: antagonists & inhibitors
%K Receptors, Interleukin-6: metabolism
%K Female
%K Antibodies, Monoclonal, Humanized: therapeutic use
%K Antibodies, Monoclonal, Humanized: pharmacology
%K Middle Aged
%K Apoptosis: drug effects
%K Aged
%K Myocytes, Cardiac: metabolism
%K Myocytes, Cardiac: drug effects
%K Transcriptome
%K Suppressor of Cytokine Signaling 3 Protein: metabolism
%K Suppressor of Cytokine Signaling 3 Protein: genetics
%K Apoptosis (Other)
%K Chemotaxis (Other)
%K Interleukin 6 (Other)
%K Interleukin inhibition (Other)
%K Monocytes (Other)
%K Myocardial infarction (Other)
%K Suppressor of cytokine signalling 3 (Other)
%K tocilizumab (NLM Chemicals)
%K Receptors, Interleukin-6 (NLM Chemicals)
%K Antibodies, Monoclonal, Humanized (NLM Chemicals)
%K Suppressor of Cytokine Signaling 3 Protein (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:41076990
%2 pmc:PMC12547449
%R 10.1016/j.ebiom.2025.105960
%U https://pub.dzne.de/record/282292