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Sci Rep. 2017 Jul 31;7(1):6877. doi: 10.1038/s41598-017-07328-z.

IL-4 as a Repurposed Biological Drug for Myocardial Infarction through Augmentation of Reparative Cardiac Macrophages: Proof-of-Concept Data in Mice.

Author information

1
William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, London, United Kingdom.
2
Cardiovascular Surgery, Kurume University, Fukuoka, Japan.
3
William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, London, United Kingdom. ken.suzuki@qmul.ac.uk.

Abstract

Recent research has shown that reparative (alternatively activated or M2) macrophages play a role in repair of damaged tissues, including the infarcted hearts. Administration of IL-4 is known to augment M2 macrophages. This translational study thus aimed to investigate whether IL-4 administration is useful for the treatment of myocardial infarction. Long-acting IL-4 complex (IL-4c; recombinant IL-4 mixed with anti-IL-4 monoclonal antibody as a stabilizer) was administered after coronary artery ligation in mice. It was observed that IL-4c administration increased accumulation of CD206+F4/80+ M2-like macrophages predominantly in the injured myocardium, compared to the control. Sorted cardiac M2-like macrophages highly expressed wide-ranging tissue repair-related genes. Indeed, IL-4c administration enhanced cardiac function in association with reduced infarct size and enhanced tissue repair (strengthened connective tissue formation, improved microvascular formation and attenuated cardiomyocyte hypertrophy). Experiments using Trib1 -/- mice that had a depleted ability to develop M2 macrophages and other in-vitro studies supported that these IL-4-mediated effects were induced via M2-like macrophages. On the other hand, when administered at Day 28 post-MI, the effects of IL-4c were diminished, suggesting a time-frame for IL-4 treatment to be effective. These data represent proof-of-concept of efficacy of IL-4 treatment for acute myocardial infarction, encouraging its further development.

PMID:
28761077
PMCID:
PMC5537273
DOI:
10.1038/s41598-017-07328-z
[Indexed for MEDLINE]
Free PMC Article

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