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Tocilizumab increases citrullinated histone 3 in non-ST segment elevation myocardial infarction

Ragnhild Helseth1, Ola Kleveland2, Thor Ueland3,4,5

  • 1Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway ragnhild.helseth@gmail.com.

Open Heart
|May 11, 2021
PubMed

Insights

Tocilizumab treatment in non-ST segment elevation myocardial infarction (NSTEMI) patients increased neutrophil extracellular trap (NET) marker H3Cit, suggesting enhanced NETosis. Myocardial injury marker troponin T (TnT) correlated with dsDNA, regardless of treatment.

Area of Science:

  • Cardiovascular Medicine
  • Immunology
  • Pharmacology

Background:

  • Tocilizumab, an interleukin-6 receptor antagonist, reduces inflammation and troponin T (TnT) release in non-ST segment elevation myocardial infarction (NSTEMI).
  • Tocilizumab also reduces neutrophil counts in NSTEMI patients, but the mechanism, particularly concerning neutrophil extracellular traps (NETs), remains unclear.

Purpose of the Study:

  • To investigate the effect of tocilizumab on NET formation markers in patients with NSTEMI.
  • To explore the relationship between NET markers, neutrophil counts, and myocardial injury.

Main Methods:

  • A placebo-controlled trial involving 117 NSTEMI patients randomized to tocilizumab or placebo before coronary angiography.
  • Measurement of NET markers (dsDNA, MPO-DNA, H3Cit) at multiple time points during hospitalization.

Main Results:

  • Circulating H3Cit levels were significantly higher in the tocilizumab group compared to placebo at all time points.
  • No significant difference in MPO-DNA or dsDNA levels between groups.
  • dsDNA levels correlated with TnT levels in both groups, indicating a link between extracellular nuclear material and myocardial injury.

Conclusions:

  • Tocilizumab treatment in NSTEMI patients is associated with increased H3Cit, suggesting enhanced NETosis.
  • Further research is needed to determine if NETosis is a significant side effect of tocilizumab.
  • dsDNA is linked to TnT release, highlighting the role of extracellular nuclear material in myocardial injury independently of tocilizumab treatment.
Abstract

Keywords:
coronary artery diseaseinflammationmyocardial infarction

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