Journal Article

DZNE-2025-01262

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The effects of interleukin-6-receptor inhibition on monocytes in STEMI: a substudy of the ASSAIL-MI trial.

Huse, C. ; Murphy, S. L. ; Yang, K. ; Balzer, N. R.DZNE* ; Stokke, M. K. ; Anstensrud, A. K. ; Bjerkeli, V. ; Rentz, T. ; Jha, P. K. ; Ugland, H. K. ; Michelsen, A. E. ; Ueland, T. ; Holm, S. ; Tøllefsen, I. M. ; Bendz, B. ; Kleveland, O. ; Andersen, G. Ø. ; Gullestad, L. ; Louch, W. E. ; Woxholt, S. ; Osnes, L. ; Broch, K. ; Ulas, T.DZNE* ; Aukrust, P. ; Libby, P. ; Halvorsen, B. ; Dahl, T. B.

2025
Elsevier Amsterdam [u.a.]

This record in other databases:    

Please use a persistent id in citations: doi:10.1016/j.ebiom.2025.105960

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.

Keyword(s): Humans (MeSH) ; Monocytes: metabolism (MeSH) ; Monocytes: drug effects (MeSH) ; ST Elevation Myocardial Infarction: drug therapy (MeSH) ; ST Elevation Myocardial Infarction: metabolism (MeSH) ; ST Elevation Myocardial Infarction: blood (MeSH) ; Male (MeSH) ; Receptors, Interleukin-6: antagonists & inhibitors (MeSH) ; Receptors, Interleukin-6: metabolism (MeSH) ; Female (MeSH) ; Antibodies, Monoclonal, Humanized: therapeutic use (MeSH) ; Antibodies, Monoclonal, Humanized: pharmacology (MeSH) ; Middle Aged (MeSH) ; Apoptosis: drug effects (MeSH) ; Aged (MeSH) ; Myocytes, Cardiac: metabolism (MeSH) ; Myocytes, Cardiac: drug effects (MeSH) ; Transcriptome (MeSH) ; Suppressor of Cytokine Signaling 3 Protein: metabolism (MeSH) ; Suppressor of Cytokine Signaling 3 Protein: genetics (MeSH) ; Apoptosis ; Chemotaxis ; Interleukin 6 ; Interleukin inhibition ; Monocytes ; Myocardial infarction ; Suppressor of cytokine signalling 3 ; tocilizumab ; Receptors, Interleukin-6 ; Antibodies, Monoclonal, Humanized ; Suppressor of Cytokine Signaling 3 Protein

---

Contributing Institute(s):

1. Clinical Single Cell Omics (CSCO) / Systems Medicine (AG Schultze)

Research Program(s):

1. 354 - Disease Prevention and Healthy Aging (POF4-354) (POF4-354)

Appears in the scientific report 2025

---

Database coverage:
; ; ; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---