Interleukin-6 inhibition in ST-elevation myocardial infarction: Immune cell profile in the randomised ASSAIL-MI trial
Camilla Huse, Anne Kristine Anstensrud, Annika E. 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 Halvorsen, Lars Gullestad, Ingebjørg Seljeflot, Pål Aukrust, Liv Osnes, Tuva B. Dahl
Abstract
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: 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 function in STEMI patients potentially related to the beneficial effects of tocilizumab on myocardial salvage. FUNDING: South-Eastern Norway Regional Health Authority (Nos. 2019067, 2017084), the Central Norway Regional Health Authority and Norwegian Research Council (No. 283867).