Interleukin-6 inhibition in ST-elevation myocardial infarction: Immune cell profile in the randomised ASSAIL-MI trial
Huse, Camilla; Anstensrud, Anne Kristine; Michelsen, Annika Elisabet; Ueland, Thor; Broch, Kaspar; Woxholt, Sindre; Yang, Kuan; Sharma, Kapil Kishore; Tøllefsen, Ingvild Maria; Bendz, Bjørn; Amundsen, Brage H.; Damås, Jan Kristian; Berg, Erlend Sturle; Bjørkelund, Elisabeth; Quiles-Jiménez, Ana M T; Bjerkeli, Vigdis; Bendz, Christina; Kleveland, Ola; Stensæth, Knut Haakon; Opdahl, Anders; Kløw, Nils-Einar; Andersen, Geir Øystein; Wiseth, Rune; Halvorsen, Bente; Gullestad, Lars; Seljeflot, Ingebjørg; Aukrust, Pål; Osnes, Liv T. N.; Dahl, Tuva Børresdatter
Peer reviewed, Journal article
Published version
Date
2022Metadata
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Abstract
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 function in STEMI patients potentially related to the beneficial effects of tocilizumab on myocardial salvage.