Interleukin-6 inhibition in ST-elevation myocardial infarction: Immune cell profile in the randomised ASSAIL-MI trial

作者：Camilla Huse, Anne Kristine Anstensrud, Annika Elisabet Michelsen, Thor Ueland, Kaspar Broch, Sindre Woxholt, Kuan Yang, Kapil Sharma, Ingvild Maria Tøllefsen, Bjørn Bendz, Brage H. Amundsen, Jan Kristian Damås, Erlend Sturle Berg, Elisabeth Bjørkelund, Ana Quiles‐Jiménez, Vigdis Bjerkeli, Christina Bendz, Ola Kleveland, Knut Haakon Stensæth, Anders Opdahl, Nils‐Einar Kløw, Geir Øystein Andersen, Rune Wiseth, Bente Lise Halvorsen, Lars Lysgaard Gullestad, Ingebjørg Seljeflot, Pål Aukrust, Liv Osnes, Tuva Børresdatter Dahl · 发表于：EBioMedicine · 年份：2022 · DOI：10.1016/j.ebiom.2022.104013 · 被引用次数：56 · 研究领域：Cardiac Fibrosis and Remodeling、Atherosclerosis and Cardiovascular Diseases、Acute Myocardial Infarction Research

Background We recently showed that interleukin (IL)-6 inhibition by tocilizumab improves myocardial salvage in ST-elevation myocardial infarction (STEMI). However, the mechanisms for this effect are not clear. Methods In this exploratory sub-study of the ASSAIL-MI trial, we examined leukocyte differential counts and their relation to myocardial salvage and peak troponin T (TnT) in STEMI patients randomised to tocilizumab ( n = 101) or placebo ( n = 98). We performed RNA-sequencing on whole blood ( n = 40) and T cells ( n = 20). B and T cell subpopulations were examined by flow cytometry ( n = 69). Findings (i) STEMI patients had higher neutrophil counts at hospitalisation compared with stable angina patients. (ii) After percutaneous coronary intervention there was a gradual decline in neutrophils, which was significantly more pronounced in the tocilizumab group. (iii) The decrease in neutrophils in the tocilizumab group was associated with improved myocardial salvage and lower peak TnT. (iv) RNA-sequencing suggested that neutrophil function was also attenuated by tocilizumab. (v) B and T cell sub-populations changed only minimally after STEMI with minor effects of tocilizumab, supported as well by RNA-sequencing analyses of T cells. (vi) However, a low CD8 + count was associated with improved myocardial salvage in patients admitted to the hospital > 3 h after symptom onset. Interpretation Tocilizumab induced a rapid reduction in neutrophils and seemed to attenuate neutrophil ...