What is the clinical evidence from this study?

Study design: RCT. Population: ST-elevation myocardial infarction (STEMI) (n=199). Intervention: Tocilizumab vs. Placebo. Primary outcome: Monocyte counts and transcriptome profile (exploratory sub-study).

What does this research mean for the field?

Interleukin-6 receptor inhibition by tocilizumab during STEMI reduces monocyte counts and induces cardioprotective alterations in monocyte signaling, potentially through the downregulation of SOCS3. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

October 11, 2025Open Access

The effects of interleukin-6-receptor inhibition on monocytes in STEMI: a substudy of the ASSAIL-MI trial

Key Result

Tocilizumab attenuated the post-PCI increase in monocyte counts and modulated cytokine signaling pathways related to myocardial remodeling, apoptosis, and chemotaxis in patients with STEMI.

Study Design

Type

RCT (n=199)

Blinding

Placebo-controlled

Randomization

1:1

Multicenter

Yes

Structured PICO

Does a single dose of intravenous tocilizumab reduce monocyte counts and alter monocyte signaling in patients with acute STEMI undergoing PCI?

Population

199 patients with STEMI and symptom onset less than 6 hours before PCI, randomized to a single dose of tocilizumab or placebo, followed for 6 months.

Intervention

Single dose of intravenous tocilizumab 280 mg administered before or simultaneously with PCI.

Comparator

Placebo administered before or simultaneously with PCI. Both groups received standard background therapy including dual antiplatelet therapy and intravenous unfractionated heparin.

Outcome

Myocardial salvage index (MSI) defined as [(area at risk - infarct size)/area at risk] x 100 assessed by MRI 3-7 days after intervention (main trial). This sub-study focused on circulating monocyte counts and transcriptome profile at 24 h and 3-7 days.surrogate

IL-6 receptor inhibition with tocilizumab in STEMI patients attenuates the acute increase in monocytes and modulates cardioprotective signaling pathways, providing a potential mechanism for its benefit on myocardial salvage.

Limitations

Low percentage of women in the trial prevented gender matching in monocyte transcriptome analyses
Monocyte isolation was only performed at one center due to personnel requirements
Small sample size for RNA sequencing analyses (n=14)

Abstract

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: 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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