Research Paper|Volume 12, Issue 20|pp 20184—20197

Interleukin-6 knockout reverses macrophage differentiation imbalance and alleviates cardiac dysfunction in aging mice

Yuan Wang¹, Shan Zhu¹, Wen Wei¹, Yi Tu¹, Chuang Chen¹, Junlong Song¹, Juanjuan Li¹, Changhua Wang², Zhiliang Xu¹, Shengrong Sun¹

¹Department of Thyroid Breast Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China
²Basic Medical School of Wuhan University, Wuhan 430060, China

* Equal contribution

Received: February 21, 2020Accepted: June 1, 2020Published: October 25, 2020

https://doi.org/10.18632/aging.103749

Copyright: © 2020 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Several interleukins (ILs) have been shown to be involved in aging, but the effects of IL-6 on aging-related cardiac dysfunction remain unknown. In this study, the expression and sources of cardiac IL-6 in aging hearts were investigated for the first time. The results showed that cardiac IL-6 expression in mice gradually increased with age, and the expression at 16 months, 20 months and 25 months was higher than that at 3 months. In addition, cardiac macrophages (Møs) were shown to be the main sources of IL-6 in aging mice. IL-6 knockout (KO) significantly alleviated cardiac dysfunction, increased M2 macrophage (Mø2) differentiation, reduced M1 macrophage (Mø1) differentiation and protected against cardiomyocyte apoptosis in aging mice. IL-6 KO also reversed the stimulatory effect of doxorubicin (DOX) treatment on Mø1s and the inhibitory effect of DOX treatment on Mø2s in vitro. Furthermore, the mRNA expression of both aging markers and apoptosis-related markers was markedly inhibited by IL-6 KO. Our results suggest that aging can be significantly reversed by IL-6 KO and that the mechanisms of this effect are related to alleviation of Mø1/Mø2 imbalance and protection against apoptosis in cardiomyocytes.