RT Journal Article SR Electronic T1 Tocilizumab increases citrullinated histone 3 in non-ST segment elevation myocardial infarction JF Open Heart JO Open Heart FD British Cardiovascular Society SP e001492 DO 10.1136/openhrt-2020-001492 VO 8 IS 1 A1 Ragnhild Helseth A1 Ola Kleveland A1 Thor Ueland A1 Rune Wiseth A1 Jan Kristian Damas A1 Kaspar Broch A1 Annika Michelsen A1 Bjørn Bendz A1 Lars Gullestad A1 Pål Aukrust A1 Ingebjørg Seljeflot YR 2021 UL http://openheart.bmj.com/content/8/1/e001492.abstract AB Objective Beyond reducing inflammation and troponin T (TnT) release, the interleukin-6 receptor antagonist tocilizumab reduces neutrophil counts in patients with non-ST segment elevation myocardial infarction (NSTEMI). It is unclear if this is related to formation of neutrophil extracellular traps (NETs), carrying inflammatory and thrombotic properties.Methods In a placebo-controlled trial, 117 patients with NSTEMI were randomised to a single dose of tocilizumab (n=58) or placebo (n=59) before coronary angiography. The NETs related markers double-stranded DNA (dsDNA), myloperoxidase–DNA (MPO–DNA) and citrullinated histone 3 (H3Cit) were measured at five consecutive time points during hospitalisation (days 1–3).Results Our major findings were: (1) H3Cit levels were significantly higher in the tocilizumab compared with the placebo group at all time points (all p<0.05), and H3Cit area under the curve (AUC) was 2.3 fold higher in the tocilizumab compared with placebo group (p<0.0001). (2) MPO–DNA and dsDNA did not differ between the groups. (3) In both treatment arms, dsDNA AUC was associated with TnT AUC. (4) Neutrophil count AUC correlated inversely to H3Cit AUC (p=0.015) in the total population.Conclusions In patients with NSTEMI, treatment with tocilizumab is associated with increased circulating H3Cit levels, suggesting that tocilizumab enhances NETosis. Further studies should clarify whether NETosis is a relevant side effect of tocilizumab. Regardless of tocilizumab, dsDNA associated with TnT release, indicating a link between extracellular nuclear material and myocardial injury.All data are in a repository at Department of Cardiology, Oslo University Hospital and are available upon reasonable request.