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Int J Cardiol. 2018 Nov 15;271:1-7. doi: 10.1016/j.ijcard.2018.04.136. Epub 2018 Jun 29.

Interleukin-6 receptor inhibition with tocilizumab induces a selective and substantial increase in plasma IP-10 and MIP-1β in non-ST-elevation myocardial infarction.

Author information

1
Clinic of Cardiology, St. Olavs Hospital, Trondheim, Norway; Department of Circulation and Medical Imaging, Norwegian University of Science and Technology NTNU, Trondheim, Norway. Electronic address: ola.kleveland@stolav.no.
2
Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Norway; Institute of Clinical Medicine, University of Oslo, Norway; K.G. Jebsen Centre of Inflammatory Research, University of Oslo, Norway; K.G. Jebsen Cardiac Research Centre, University of Oslo, Norway.
3
Institute of Clinical Medicine, University of Oslo, Norway; Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
4
Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Norway; Institute of Clinical Medicine, University of Oslo, Norway; Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
5
Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Norway; Institute of Clinical Medicine, University of Oslo, Norway; K.G. Jebsen Centre of Inflammatory Research, University of Oslo, Norway; Centre for Heart Failure Research, University of Oslo, Norway.
6
K.G. Jebsen Cardiac Research Centre, University of Oslo, Norway; Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
7
Clinic of Cardiology, St. Olavs Hospital, Trondheim, Norway; Department of Circulation and Medical Imaging, Norwegian University of Science and Technology NTNU, Trondheim, Norway.
8
Centre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology NTNU, Trondheim, Norway.
9
Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
10
Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Norway.
11
Centre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology NTNU, Trondheim, Norway; K.G. Jebsen Centre of Inflammatory Research, University of Oslo, Norway; Department of Immunology, Oslo University Hospital Rikshospitalet, Oslo, Norway; Research laboratory, Nordland Hospital, Bodø, Norway; Faculty of Health Sciences, K.G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Tromsø, Norway.
12
Institute of Clinical Medicine, University of Oslo, Norway; K.G. Jebsen Cardiac Research Centre, University of Oslo, Norway; Centre for Heart Failure Research, University of Oslo, Norway; Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
13
Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Norway; Institute of Clinical Medicine, University of Oslo, Norway; K.G. Jebsen Centre of Inflammatory Research, University of Oslo, Norway.

Abstract

AIM:

To evaluate the effect of interleukin-6 inhibition with tocilizumab on the cytokine network in patients with acute non-ST-elevation myocardial infarction (NSTEMI).

METHODS:

117 patients with acute NSTEMI were randomised to an intravenous infusion of 280 mg tocilizumab or placebo prior to coronary angiography. Blood samples were obtained at baseline, at 6 consecutive points in time during hospitalisation, and at follow-up after 3 and 6 months. Cytokines (n = 27) were analysed with a multiplex cytokine assay.

RESULTS:

Using a mixed between-within subjects analysis of variance, we observed a significant (p < 0.001) between-group difference in changes for interferon gamma-inducible protein (IP-10) and macrophage inflammatory protein-1β (MIP-1β), due to significant increases in the tocilizumab group during hospitalisation (i.e., IP-10 median change from baseline during hospitalisation (mΔ), placebo: 3 (-60, 68) pg/ml vs tocilizumab: 209 (69, 335) pg/ml; MIP-1β mΔ, placebo: 5 (-2, 12) pg/ml vs tocilizumab: 39 (24, 63) pg/ml). MIP-1β was inversely correlated to troponin T (r = -0.28, p < 0.05) and neutrophils (r = -0.32, p < 0.05) in the tocilizumab group. In contrast, tocilizumab had only modest or no effects on the other examined cytokines.

CONCLUSIONS:

Tocilizumab led to a selective and substantial increase in IP-10 and MIP-1β during the acute phase of NSTEMI, with no or only minor effects on the other measured cytokines. ClinicalTrials.gov, NCT01491074.

KEYWORDS:

IP-10; Inflammation; Interleukin-6; MIP-1β; Myocardial infarction; Tocilizumab

Comment in

PMID:
29961572
DOI:
10.1016/j.ijcard.2018.04.136
[Indexed for MEDLINE]

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