Sex Dimorphism in Muscle Damage–induced Inflammation

Abstract

Introduction:The purpose of this study was to determine the effect of resistance exercise (RE)-induced hormonal changes on intramuscular cytokine gene expression after muscle damage in untrained men and women. Methods: Men (n = 8, 22 ± 3 yr) and women (n = 8, 19 ± 1 yr) completed two sessions of 80 unilateral maximal eccentric knee extensions followed by either an upper body RE bout (EX) or a time-matched period (CON). Muscle samples (vastus laterals) were analyzed for mRNA expression of interleukin (IL) 6, IL-10, IL-15, TNFA, TGFB, CCL2, and CD68 at PRE, 12 h, and 24 h after the session. Results: A significant time-sex-condition interaction was found for TGFB with an increase for EX in men at 12 h from PRE. For EX, TGFB was also greater in men than in women at 12 and 24 h. Significant time-sex and condition-sex interactions were found for IL-10 with an increase for men that was greater than for women at 12 and 24 h. IL-10 was lower in EX than CON for men. A significant time-sex interaction was found for TNFA with an increase for men that was greater than for women at 24 h. A significant time-condition interaction was found for CD68 with an increase at 12 h and decrease at 24 h for EX and CON. CD68 was lower in EX than CON at 12 h. A significant time effect was found for IL6 and CCL2 with an increase at 12 and 24 h. Conclusions: Results suggest that women seem to have a muted intramuscular cytokine (i.e., IL-10, TNF-α, and TGF-β) response to muscle damage compared with men.

Differential Autophagy Response in Men and Women After Muscle Damage

“…Since autophagy is critical to tag and to engulf damaged protein for degradation, the different autophagy responses between sexes could be due to a greater demand for degrading damaged protein in men. In accordance, we had previously reported that with the same relative total work performed, CK was greater for men than women at 12 h and with a similar trend at 24 h (Luk et al, 2021). The degree of muscle damage might, at least partly, explain the increase in autophagosome degradation observed in men but not in women at 24 h. With the importance of autophagy in muscle regeneration, the lack of change in autophagy for women could be interpreted to negatively impact muscle recovery.…”

“…To confirm muscle damage, serum creatine kinase (CK) activity was measured immediately after the maximal effort unilateral eccentric knee extension exercise (IMD; CK is not expected to differ from baseline at this time point) and at 12 h and 24 h after completion of the upper body RE or 20 min rest. The CK results have been reported previously ( Luk et al, 2021 ). Briefly, CK was significantly greater (1.6-fold) at 12 h in men than women.…”

“…Written informed consent was obtained from each subject before participation in the study. The details of the study protocol and subjects demographic have been published previously ( Luk et al, 2021 ). Briefly, due to the limited muscle samples, a subset of the sixteen healthy young untrained men ( n = 8; 22 ± 3; 180.1 ± 5.7 cm height; 80.8 ± 15.6 kg body mass; 26.6 ± 10.3% mean body fat) and women ( n = 8; 20 ± 1; 164.1 ± 9.0 cm height; 60.7 ± 7.8 kg body mass; 34.7 ± 9.1% mean body fat) was used for this report.…”

“…Details of muscle tissue homogenization and RNA isolation have been published previously ( Luk et al, 2021 ). After removing visually apparent fascia and adipose, RNA was isolated from flash frozen muscle samples (∼30 mg) using the RNeasy Fibrous Tissue Mini Kit (Cat.…”

“…To date, studies have demonstrated that men and women respond differently to muscle damage, such as the degree of muscle damage and the response of cytokines ( Luk et al, 2021 ). Autophagy and its interaction with cytokines are critical to muscle regeneration ( Lira et al, 2013 ; Paré et al, 2017 ; Ge et al, 2018 ) and testosterone and glucocorticoids (e.g., cortisol) differentially regulate autophagic activity ( Shimizu et al, 2011 ; Serra et al, 2013 ; White et al, 2013 ).…”