Open Heart (Jul 2023)

Cytokine pattern in patients with ST-elevation myocardial infarction treated with the interleukin-6 receptor antagonist tocilizumab

  • Ola Kleveland,
  • Rune Wiseth,
  • Jan Kristian Damås,
  • Pål Aukrust,
  • Lars Gullestad,
  • Bente Halvorsen,
  • Einar Hopp,
  • Kaspar Broch,
  • T Ueland,
  • Anne Kristine Anstensrud,
  • Sindre Woxholt,
  • Bjørn Bendz,
  • Brage H Amundsen,
  • Nils-Einar Kløw,
  • Ingebjørg Seljeflot,
  • Geir Øystein Andersen,
  • Ingvild Maria Tøllefsen,
  • Liv Ryan,
  • Tuva B Dahl,
  • Camilla Huse

DOI
https://doi.org/10.1136/openhrt-2023-002301
Journal volume & issue
Vol. 10, no. 2

Abstract

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Background Tocilizumab improves myocardial salvage index (MSI) in patients with ST-elevation myocardial infarction (STEMI), but its mechanisms of action are unclear. Here, we explored how cytokines were affected by tocilizumab and their correlations with neutrophils, C-reactive protein (CRP), troponin T, MSI and infarct size.Methods STEMI patients were randomised to receive a single dose of 280 mg tocilizumab (n=101) or placebo (n=98) before percutaneous coronary intervention. Blood samples were collected before infusion of tocilizumab or placebo at baseline, during follow-up at 24–36, 72–168 hours, 3 and 6 months. 27 cytokines were analysed using a multiplex cytokine assay. Cardiac MRI was performed during hospitalisation and 6 months.Results Repeated measures analysis of variance showed significant (p<0.001) between-group difference in changes for IL-6, IL-8 and IL-1ra due to an increase in the tocilizumab group during hospitalisation. IL-6 and IL-8 correlated to neutrophils in the placebo group (r=0.73, 0.68, respectively), which was attenuated in the tocilizumab group (r=0.28, 0.27, respectively). A similar pattern was seen for MSI and IL-6 and IL-8 in the placebo group (r=−0.29, –0.25, respectively) in patients presenting ≤3 hours from symptom onset, which was attenuated in the tocilizumab group (r=−0.09,–0.14, respectively).Conclusions Tocilizumab increases IL-6, IL-8 and IL-1ra in STEMI. IL-6 and IL-8 show correlations to neutrophils/CRP and markers of cardiac injury in the placebo group that was attenuated in the tocilizumab group. This may suggest a beneficial effect of tocilizumab on the ischaemia-reperfusion injury in STEMI patients.Trial registration number NCT03004703.