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

Antibodies, Monoclonal, Humanized / pharmacology Humans Interleukin-6 / antagonists & inhibitors Leukocytes / drug effects Lymphocyte Count Myocardium Neutrophils / drug effects Percutaneous Coronary Intervention / adverse effects RNA Randomized Controlled Trials as Topic ST Elevation Myocardial Infarction / blood T-Lymphocyte Subsets / drug effects Treatment Outcome
Inflammation Interleukin-6 Lymphocytes Neutrophils ST-elevation myocardial infarction Tocilizumab

Journal

EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039

Informations de publication

Date de publication:
Jun 2022
Historique:
received: 07 12 2021
revised: 02 04 2022
accepted: 05 04 2022
pubmed: 4 5 2022
medline: 15 6 2022
entrez: 3 5 2022
Statut: ppublish

Résumé

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. 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). (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 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. South-Eastern Norway Regional Health Authority (Nos. 2019067, 2017084), the Central Norway Regional Health Authority and Norwegian Research Council (No. 283867).

Sections du résumé

BACKGROUND 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 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 RESULTS
(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
INTERPRETATION CONCLUSIONS
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 BACKGROUND
South-Eastern Norway Regional Health Authority (Nos. 2019067, 2017084), the Central Norway Regional Health Authority and Norwegian Research Council (No. 283867).

Identifiants

DOI: 10.1016/j.ebiom.2022.104013 PMID: 35504178 PMC: PMC9079006
pubmed: 35504178
pii: S2352-3964(22)00197-9
doi: 10.1016/j.ebiom.2022.104013
pmc: PMC9079006
pii:
doi:

Substances chimiques

Antibodies, Monoclonal, Humanized 0
Interleukin-6 0
RNA 63231-63-0
tocilizumab I031V2H011

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

104013

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.

Références

Front Immunol. 2021 May 05;12:605857
pubmed: 34046028
Cardiol J. 2014;21(5):500-8
pubmed: 24142685
Circ Res. 2015 Jan 30;116(3):489-503
pubmed: 25634972
Am J Physiol Heart Circ Physiol. 2000 Dec;279(6):H2954-60
pubmed: 11087252
Nat Genet. 2003 Jul;34(3):267-73
pubmed: 12808457
Eur Heart J. 2016 Aug 07;37(30):2406-13
pubmed: 27161611
Open Heart. 2019 Oct 15;6(2):e001108
pubmed: 31673391
Nucleic Acids Res. 2019 Jan 8;47(D1):D766-D773
pubmed: 30357393
Nat Commun. 2019 Apr 3;10(1):1523
pubmed: 30944313
J Exp Med. 2016 Oct 17;213(11):2281-2291
pubmed: 27670591
Oxid Med Cell Longev. 2018 Mar 18;2018:1975167
pubmed: 29743973
Nat Biotechnol. 2019 Jul;37(7):773-782
pubmed: 31061481
J Am Coll Cardiol. 2021 Apr 20;77(15):1845-1855
pubmed: 33858620
Immunity. 2019 Apr 16;50(4):1007-1023
pubmed: 30995492
Eur Heart J. 2018 Oct 7;39(38):3499-3507
pubmed: 30165610
Int Immunopharmacol. 2013 Nov;17(3):638-50
pubmed: 23994464
Genome Biol. 2014;15(12):550
pubmed: 25516281
Sci Rep. 2020 Apr 14;10(1):6271
pubmed: 32286338
Rev Assoc Med Bras (1992). 2020 Jul;66(7):954-959
pubmed: 32844936
PLoS Comput Biol. 2020 Feb 25;16(2):e1007664
pubmed: 32097405
Circulation. 2020 Nov 17;142(20):1996-1998
pubmed: 32864998
Br J Clin Pharmacol. 2020 Jul;86(7):1387-1397
pubmed: 32067256
Immunol Rev. 2016 Sep;273(1):121-39
pubmed: 27558332
Bioinformatics. 2018 Sep 1;34(17):i884-i890
pubmed: 30423086
Nat Rev Drug Discov. 2021 Aug;20(8):589-610
pubmed: 33976384
Genome Res. 2003 Nov;13(11):2498-504
pubmed: 14597658
Nucleic Acids Res. 2020 Jan 8;48(D1):D498-D503
pubmed: 31691815
Open Heart. 2021 May;8(1):
pubmed: 33972404
N Engl J Med. 2020 Nov 5;383(19):1838-1847
pubmed: 32865380
J Clin Med. 2020 May 25;9(5):
pubmed: 32466264
Heart Fail Rev. 2018 Sep;23(5):733-758
pubmed: 29862462
Thromb Haemost. 2011 Oct;106(4):591-9
pubmed: 21866299
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Cell Signal. 2021 Jan;77:109816
pubmed: 33122000
Nat Immunol. 2015 May;16(5):448-57
pubmed: 25898198
J Cardiol. 2019 Jan;73(1):22-27
pubmed: 29907363
Antioxid Redox Signal. 2020 Oct 1;33(10):689-712
pubmed: 32517486
Small GTPases. 2019 May;10(3):187-195
pubmed: 28328290
J Clin Invest. 2015 Aug 3;125(8):3063-76
pubmed: 26168217
Circ Res. 2004 Jun 25;94(12):1543-53
pubmed: 15217919
Nat Methods. 2017 Apr;14(4):417-419
pubmed: 28263959
Cell Mol Immunol. 2021 Feb;18(2):374-384
pubmed: 33420357

Auteurs

Camilla Huse (C)

Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Anne Kristine Anstensrud (AK)

Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Annika E Michelsen (AE)

Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Thor Ueland (T)

Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; K. G. Jebsen Thrombosis Research and Expertise Centre (TREC), The Arctic University of Norway, Tromsø, Norway.

Kaspar Broch (K)

Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway; K. G. Jebsen Cardiac Research Centre and Centre for Heart Failure Research, University of Oslo, Oslo, Norway.

Sindre Woxholt (S)

Clinic of Cardiology, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway; Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.

Kuan Yang (K)

Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Kapil Sharma (K)

Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway.

Ingvild Maria Tøllefsen (IM)

Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway.

Bjørn Bendz (B)

Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Brage Høyem Amundsen (BH)

Clinic of Cardiology, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway; Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.

Jan Kristian Damås (JK)

Department of Infectious Disease, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway; Department of Clinical and Molecular Medicine, Centre of Molecular Inflammation Research, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.

Erlend Sturle Berg (ES)

Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway.

Elisabeth Bjørkelund (E)

Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway.

Ana Quiles-Jiménez (A)

Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Vigdis Bjerkeli (V)

Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Christina Bendz (C)

Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway.

Ola Kleveland (O)

Clinic of Cardiology, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway; Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.

Knut Haakon Stensaeth (KH)

Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Department of Radiology and Nuclear Medicine, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway.

Anders Opdahl (A)

Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway.

Nils-Einar Kløw (NE)

Department of Radiology, Oslo University Hospital Ullevål, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Geir Øystein Andersen (GØ)

Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway; Department of Cardiology, Center for Clinical Heart Research, Oslo University Hospital Ullevål, Oslo, Norway.

Rune Wiseth (R)

Clinic of Cardiology, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway; Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.

Bente Halvorsen (B)

Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Lars Gullestad (L)

Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway; K. G. Jebsen Cardiac Research Centre and Centre for Heart Failure Research, University of Oslo, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Ingebjørg Seljeflot (I)

Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Cardiology, Center for Clinical Heart Research, Oslo University Hospital Ullevål, Oslo, Norway.

Pål Aukrust (P)

Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Rheumatology, Dermatology and Infectious Disease, Oslo University Hospital Rikshospitalet, Oslo, Norway.

Liv Osnes (L)

Department of Immunology, Oslo University Hospital Rikshospitalet, Oslo, Norway.

Tuva B Dahl (TB)

Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Department of Research and Development, Division of Emergencies and Critical Care, Oslo University Hospital, Norway. Electronic address: tuvad@medisin.uio.no.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps monoclonaux › Anticorps monoclonaux humanisés › Interleukin-6 inhibition in ST-elevation...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Interleukin-6 inhibition in ST-elevation...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Interleukines › Interleukine-6 › Interleukin-6 inhibition in ST-elevation...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Interleukin-6 inhibition in ST-elevation...
questionsmedicales.fr › Phénomènes physiologiques respiratoires et circulatoires › Phénomènes physiogiques du sang › Hémogramme › Numération des leucocytes › Numération des lymphocytes › Interleukin-6 inhibition in ST-elevation...
questionsmedicales.fr › Tissus › Muscles › Muscle strié › Myocarde › Interleukin-6 inhibition in ST-elevation...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Phagocytes › Granulocytes neutrophiles › Interleukin-6 inhibition in ST-elevation...
questionsmedicales.fr › Procédures de chirurgie opératoire › Interventions chirurgicales mini-invasives › Procédures endovasculaires › Intervention coronarienne percutanée › Interleukin-6 inhibition in ST-elevation...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › Interleukin-6 inhibition in ST-elevation...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études cliniques comme sujet › Essais cliniques comme sujet › Essais cliniques contrôlés comme sujet › Essais contrôlés randomisés comme sujet › Interleukin-6 inhibition in ST-elevation...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Nécrose › Infarctus › Infarctus du myocarde › Infarctus du myocarde avec sus-décalage du segment ST › Interleukin-6 inhibition in ST-elevation...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Sous-populations de lymphocytes T › Interleukin-6 inhibition in ST-elevation...
questionsmedicales.fr › Qualité, accès, évaluation des soins de santé › Qualité des soins de santé › Mécanismes d'évaluation des soins de santé › Évaluation des résultats et des processus en soins de santé › Évaluation de résultat (soins) › Résultat thérapeutique › Interleukin-6 inhibition in ST-elevation...