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

EBioMedicine

Jan Kristian Damås¹  Anders Opdahl¹  Geir Øystein Andersen²  Elisabeth Bjørkelund³  Ingebjørg Seljeflot³  Ola Kleveland³  Thor Ueland³  Liv Osnes³  Sindre Woxholt³  Anne Kristine Anstensrud³  Bjørn Bendz⁴  Kapil Sharma⁵  Knut Haakon Stensaeth⁶  Brage Høyem Amundsen⁶  Ingvild Maria Tøllefsen⁷  Rune Wiseth⁷  Bente Halvorsen⁷  Tuva B. Dahl⁷  Annika E. Michelsen⁷  Christina Bendz⁷  Vigdis Bjerkeli⁸  Ana Quiles-Jiménez⁸  Nils-Einar Kløw⁹  Kaspar Broch^1,10  Pål Aukrust^1,10  Kuan Yang^1,10  Camilla Huse^1,10  Erlend Sturle Berg^1,10  Lars Gullestad^1,10 

[1] Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway;Department of Clinical and Molecular Medicine, Centre of Molecular Inflammation Research, Norwegian University of Science and Technology (NTNU), Trondheim, Norway;Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway;K. G. Jebsen Cardiac Research Centre and Centre for Heart Failure Research, University of Oslo, Oslo, Norway;K. G. Jebsen Thrombosis Research and Expertise Centre (TREC), The Arctic University of Norway, Tromsø, Norway;Clinic of Cardiology, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway;Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway;Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway;Department of Infectious Disease, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway;Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway;

关键词: ST-elevation myocardial infarction;    Neutrophils;    Lymphocytes;    Tocilizumab;    Interleukin-6;    Inflammation;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: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 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).

【 授权许可】

Unknown