TY  - JOUR
AU  - Huse, Camilla
AU  - Murphy, Sarah Louise
AU  - Yang, Kuan
AU  - Balzer, Nora Reka
AU  - Stokke, Mathis K
AU  - Anstensrud, Anne Kristine
AU  - Bjerkeli, Vigdis
AU  - Rentz, Thiago
AU  - Jha, Prabhash Kumar
AU  - Ugland, Hege Katrin
AU  - Michelsen, Annika E
AU  - Ueland, Thor
AU  - Holm, Sverre
AU  - Tøllefsen, Ingvild Maria
AU  - Bendz, Bjørn
AU  - Kleveland, Ola
AU  - Andersen, Geir Øystein
AU  - Gullestad, Lars
AU  - Louch, William E
AU  - Woxholt, Sindre
AU  - Osnes, Liv
AU  - Broch, Kaspar
AU  - Ulas, Thomas
AU  - Aukrust, Pål
AU  - Libby, Peter
AU  - Halvorsen, Bente
AU  - Dahl, Tuva B
TI  - The effects of interleukin-6-receptor inhibition on monocytes in STEMI: a substudy of the ASSAIL-MI trial.
JO  - EBioMedicine
VL  - 121
SN  - 2352-3964
CY  - Amsterdam [u.a.]
PB  - Elsevier
M1  - DZNE-2025-01262
SP  - 105960
PY  - 2025
AB  - 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.
KW  - Humans
KW  - Monocytes: metabolism
KW  - Monocytes: drug effects
KW  - ST Elevation Myocardial Infarction: drug therapy
KW  - ST Elevation Myocardial Infarction: metabolism
KW  - ST Elevation Myocardial Infarction: blood
KW  - Male
KW  - Receptors, Interleukin-6: antagonists & inhibitors
KW  - Receptors, Interleukin-6: metabolism
KW  - Female
KW  - Antibodies, Monoclonal, Humanized: therapeutic use
KW  - Antibodies, Monoclonal, Humanized: pharmacology
KW  - Middle Aged
KW  - Apoptosis: drug effects
KW  - Aged
KW  - Myocytes, Cardiac: metabolism
KW  - Myocytes, Cardiac: drug effects
KW  - Transcriptome
KW  - Suppressor of Cytokine Signaling 3 Protein: metabolism
KW  - Suppressor of Cytokine Signaling 3 Protein: genetics
KW  - Apoptosis (Other)
KW  - Chemotaxis (Other)
KW  - Interleukin 6 (Other)
KW  - Interleukin inhibition (Other)
KW  - Monocytes (Other)
KW  - Myocardial infarction (Other)
KW  - Suppressor of cytokine signalling 3 (Other)
KW  - tocilizumab (NLM Chemicals)
KW  - Receptors, Interleukin-6 (NLM Chemicals)
KW  - Antibodies, Monoclonal, Humanized (NLM Chemicals)
KW  - Suppressor of Cytokine Signaling 3 Protein (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:41076990
C2  - pmc:PMC12547449
DO  - DOI:10.1016/j.ebiom.2025.105960
UR  - https://pub.dzne.de/record/282292
ER  -