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@ARTICLE{Huse:282292,
      author       = {Huse, Camilla and Murphy, Sarah Louise and Yang, Kuan and
                      Balzer, Nora Reka and Stokke, Mathis K and Anstensrud, Anne
                      Kristine and Bjerkeli, Vigdis and Rentz, Thiago and Jha,
                      Prabhash Kumar and Ugland, Hege Katrin and Michelsen, Annika
                      E and Ueland, Thor and Holm, Sverre and Tøllefsen, Ingvild
                      Maria and Bendz, Bjørn and Kleveland, Ola and Andersen,
                      Geir Øystein and Gullestad, Lars and Louch, William E and
                      Woxholt, Sindre and Osnes, Liv and Broch, Kaspar and Ulas,
                      Thomas and Aukrust, Pål and Libby, Peter and Halvorsen,
                      Bente and Dahl, Tuva B},
      title        = {{T}he effects of interleukin-6-receptor inhibition on
                      monocytes in {STEMI}: a substudy of the {ASSAIL}-{MI}
                      trial.},
      journal      = {EBioMedicine},
      volume       = {121},
      issn         = {2352-3964},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier},
      reportid     = {DZNE-2025-01262},
      pages        = {105960},
      year         = {2025},
      abstract     = {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.},
      keywords     = {Humans / Monocytes: metabolism / Monocytes: drug effects /
                      ST Elevation Myocardial Infarction: drug therapy / ST
                      Elevation Myocardial Infarction: metabolism / ST Elevation
                      Myocardial Infarction: blood / Male / Receptors,
                      Interleukin-6: antagonists $\&$ inhibitors / Receptors,
                      Interleukin-6: metabolism / Female / Antibodies, Monoclonal,
                      Humanized: therapeutic use / Antibodies, Monoclonal,
                      Humanized: pharmacology / Middle Aged / Apoptosis: drug
                      effects / Aged / Myocytes, Cardiac: metabolism / Myocytes,
                      Cardiac: drug effects / Transcriptome / Suppressor of
                      Cytokine Signaling 3 Protein: metabolism / Suppressor of
                      Cytokine Signaling 3 Protein: genetics / Apoptosis (Other) /
                      Chemotaxis (Other) / Interleukin 6 (Other) / Interleukin
                      inhibition (Other) / Monocytes (Other) / Myocardial
                      infarction (Other) / Suppressor of cytokine signalling 3
                      (Other) / tocilizumab (NLM Chemicals) / Receptors,
                      Interleukin-6 (NLM Chemicals) / Antibodies, Monoclonal,
                      Humanized (NLM Chemicals) / Suppressor of Cytokine Signaling
                      3 Protein (NLM Chemicals)},
      cin          = {AG Schultze},
      ddc          = {610},
      cid          = {I:(DE-2719)1013038},
      pnm          = {354 - Disease Prevention and Healthy Aging (POF4-354)},
      pid          = {G:(DE-HGF)POF4-354},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41076990},
      pmc          = {pmc:PMC12547449},
      doi          = {10.1016/j.ebiom.2025.105960},
      url          = {https://pub.dzne.de/record/282292},
}