Translational overview of cytokine inhibition in acute myocardial infarction and chronic heart failure.

Autor: Hartman MHT; Department of Cardiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, the Netherlands. Electronic address: h.t.hartman@umcg.nl., Groot HE; Department of Cardiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, the Netherlands., Leach IM; Department of Cardiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, the Netherlands., Karper JC; Department of Cardiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, the Netherlands., van der Harst P; Department of Cardiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, the Netherlands.
Jazyk: angličtina
Zdroj: Trends in cardiovascular medicine [Trends Cardiovasc Med] 2018 Aug; Vol. 28 (6), pp. 369-379. Date of Electronic Publication: 2018 Feb 15.
DOI: 10.1016/j.tcm.2018.02.003
Abstrakt: Many cytokines are currently under investigation as potential target to improve cardiac function and outcome in the setting of acute myocardial infarction (MI) or chronic heart failure (HF). Here we aim to provide a translational overview of cytokine inhibiting therapies tested in experimental models and clinical studies. In various experimental studies, inhibition of interleukin-1 (IL-1), -6 (IL-6), -8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), CC- and CXC chemokines, and tumor necrosis factor-α (TNF-α) had beneficial effects on cardiac function and outcome. On the other hand, neutral or even detrimental results have been reported for some (IL-1, IL-6, IL-8, and MCP-1). Ambivalence of cytokine function, differences in study designs, treatment regimens and chosen endpoints hamper the translation of experimental research into clinical practice. Human studies are currently limited to IL-1β inhibition, IL-1 receptor antagonists (IL-1RA), IL-6 receptor antagonists (IL-6RA) or TNF inhibition. Despite favorable effects on cardiovascular events observed in retrospective cohort studies of rheumatoid arthritis patients treated with TNF inhibition or IL-1RA, most prospective studies reported disappointing and inconsistent results. Smaller studies (n < 100) generally reported favorable results of anticytokine therapy on cardiac function, but only one of the larger studies (n > 100) evaluating IL-1β inhibition presented positive results on outcome. In conclusion, of the 10 anticytokine therapies tested in animals models beneficial effects have been reported in at least one setting. In larger clinical studies, findings were unsatisfactory in all but one. Many anticytokine therapies with promising animal experimental data continue to require further evaluation in humans.
(Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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