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.

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.

• Authors: Ola Kleveland, Thor Ueland, Gabor Kunszt, Marte Bratlie, Arne Yndestad, Kaspar Broch, Espen Holte, Liv Ryan, Brage H Amundsen, Bjørn Bendz, Svend Aakhus, Terje Espevik, Bente Halvorsen, Tom E Mollnes, Rune Wiseth, Lars Gullestad, Pål Aukrust, Jan Kristian Damås
• Journal: International journal of cardiology (Int J Cardiol) Vol. 271 Pg. 1-7 (Nov 15 2018) ISSN: 1874-1754 [Electronic] Netherlands
• PMID: 29961572 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• Biomarkers
• CXCL10 protein, human
• Chemokine CCL4
• Chemokine CXCL10
• Receptors, Interleukin-6
• tocilizumab

Topics

• Aged
• Antibodies, Monoclonal, Humanized (pharmacology, therapeutic use)
• Biomarkers (blood)
• Chemokine CCL4 (blood)
• Chemokine CXCL10 (blood)
• Female
• Humans
• Male
• Middle Aged
• Non-ST Elevated Myocardial Infarction (blood, drug therapy)
• Receptors, Interleukin-6 (antagonists & inhibitors, blood)