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000282292 0247_ $$2doi$$a10.1016/j.ebiom.2025.105960
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000282292 1001_ $$aHuse, Camilla$$b0
000282292 245__ $$aThe effects of interleukin-6-receptor inhibition on monocytes in STEMI: a substudy of the ASSAIL-MI trial.
000282292 260__ $$aAmsterdam [u.a.]$$bElsevier$$c2025
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000282292 520__ $$aInterleukin-6 receptor (IL-6R) inhibition by tocilizumab improves myocardial salvage index (MSI) in ST-elevation myocardial infarction (STEMI). However, the mechanisms for this effect remain unclear.This pre-defined exploratory sub-study of the ASSAIL-MI trial enumerated circulating monocytes and examined their transcriptome profile in relation to the MSI and peak troponin T (TnT) in STEMI patients randomiseded to tocilizumab (n = 101) or placebo (n = 98). RNA sequencing was performed on peripheral monocytes in 14 patients. To elaborate the in vivo findings, in vitro chemotaxis and apoptosis assays were performed on THP-1 monocytes and cardiomyocyte (HL-1) cell lines, respectively.STEMI patients had increased monocyte counts at 24 h and 3-7 days after hospitalisation/PCI and this increase was attenuated by tocilizumab. Lower monocyte levels at 24 h were associated with lower TnT levels and higher MSI. Monocyte gene expression suggested that tocilizumab modulated cytokine signalling pathways related to myocardial remodelling, apoptosis, and chemotaxis, potentially through a decrease in suppressor of cytokine signalling 3 (SOCS3). In vitro, tocilizumab limited apoptosis of cardiomyocytes exposed to ischemia/reperfusion and reduced chemotaxis in monocytes exposed to IL-6.These findings suggest that IL-6R inhibition by tocilizumab during STEMI is associated with reduced monocyte counts and cardioprotective alterations in monocyte signalling potentially linked to the downregulation of SOCS3.This work was supported by the South-Eastern Norway Regional Health Authority (no. 2019067) and The Research Council of Norway (no. 282867) The ASSAIL-MI main study was supported by an independent grant from ROCHE who also provided drugs/placebo for infusion.
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000282292 650_7 $$2Other$$aApoptosis
000282292 650_7 $$2Other$$aChemotaxis
000282292 650_7 $$2Other$$aInterleukin 6
000282292 650_7 $$2Other$$aInterleukin inhibition
000282292 650_7 $$2Other$$aMonocytes
000282292 650_7 $$2Other$$aMyocardial infarction
000282292 650_7 $$2Other$$aSuppressor of cytokine signalling 3
000282292 650_7 $$0I031V2H011$$2NLM Chemicals$$atocilizumab
000282292 650_7 $$2NLM Chemicals$$aReceptors, Interleukin-6
000282292 650_7 $$2NLM Chemicals$$aAntibodies, Monoclonal, Humanized
000282292 650_7 $$2NLM Chemicals$$aSuppressor of Cytokine Signaling 3 Protein
000282292 650_2 $$2MeSH$$aHumans
000282292 650_2 $$2MeSH$$aMonocytes: metabolism
000282292 650_2 $$2MeSH$$aMonocytes: drug effects
000282292 650_2 $$2MeSH$$aST Elevation Myocardial Infarction: drug therapy
000282292 650_2 $$2MeSH$$aST Elevation Myocardial Infarction: metabolism
000282292 650_2 $$2MeSH$$aST Elevation Myocardial Infarction: blood
000282292 650_2 $$2MeSH$$aMale
000282292 650_2 $$2MeSH$$aReceptors, Interleukin-6: antagonists & inhibitors
000282292 650_2 $$2MeSH$$aReceptors, Interleukin-6: metabolism
000282292 650_2 $$2MeSH$$aFemale
000282292 650_2 $$2MeSH$$aAntibodies, Monoclonal, Humanized: therapeutic use
000282292 650_2 $$2MeSH$$aAntibodies, Monoclonal, Humanized: pharmacology
000282292 650_2 $$2MeSH$$aMiddle Aged
000282292 650_2 $$2MeSH$$aApoptosis: drug effects
000282292 650_2 $$2MeSH$$aAged
000282292 650_2 $$2MeSH$$aMyocytes, Cardiac: metabolism
000282292 650_2 $$2MeSH$$aMyocytes, Cardiac: drug effects
000282292 650_2 $$2MeSH$$aTranscriptome
000282292 650_2 $$2MeSH$$aSuppressor of Cytokine Signaling 3 Protein: metabolism
000282292 650_2 $$2MeSH$$aSuppressor of Cytokine Signaling 3 Protein: genetics
000282292 7001_ $$aMurphy, Sarah Louise$$b1
000282292 7001_ $$aYang, Kuan$$b2
000282292 7001_ $$0P:(DE-2719)9002224$$aBalzer, Nora Reka$$b3$$udzne
000282292 7001_ $$aStokke, Mathis K$$b4
000282292 7001_ $$aAnstensrud, Anne Kristine$$b5
000282292 7001_ $$aBjerkeli, Vigdis$$b6
000282292 7001_ $$aRentz, Thiago$$b7
000282292 7001_ $$aJha, Prabhash Kumar$$b8
000282292 7001_ $$aUgland, Hege Katrin$$b9
000282292 7001_ $$aMichelsen, Annika E$$b10
000282292 7001_ $$aUeland, Thor$$b11
000282292 7001_ $$aHolm, Sverre$$b12
000282292 7001_ $$aTøllefsen, Ingvild Maria$$b13
000282292 7001_ $$aBendz, Bjørn$$b14
000282292 7001_ $$aKleveland, Ola$$b15
000282292 7001_ $$aAndersen, Geir Øystein$$b16
000282292 7001_ $$aGullestad, Lars$$b17
000282292 7001_ $$aLouch, William E$$b18
000282292 7001_ $$aWoxholt, Sindre$$b19
000282292 7001_ $$aOsnes, Liv$$b20
000282292 7001_ $$aBroch, Kaspar$$b21
000282292 7001_ $$0P:(DE-2719)9000845$$aUlas, Thomas$$b22$$udzne
000282292 7001_ $$aAukrust, Pål$$b23
000282292 7001_ $$aLibby, Peter$$b24
000282292 7001_ $$aHalvorsen, Bente$$b25
000282292 7001_ $$aDahl, Tuva B$$b26
000282292 773__ $$0PERI:(DE-600)2799017-5$$a10.1016/j.ebiom.2025.105960$$gVol. 121, p. 105960 -$$p105960$$tEBioMedicine$$v121$$x2352-3964$$y2025
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