Time Course and Role of Exercise-Induced Cytokines in Muscle Damage and Repair After a Marathon Race.

Cesar Augustus Zocoler De Sousa,Maria Fernanda Cury-Boaventura,Bryan Steve Martínez Galán,Richelieau Manoel,Ana Paula Renno Sierra,Hermes Vieira Barbeiro,Jaqueline Fernanda De Sousa Maciel,Heraldo Possolo De Souza

doi:10.3389/fphys.2021.752144

Cesar Augustus Zocoler De Sousa, Maria Fernanda Cury-Boaventura + Show 6 more

Open Access

https://doi.org/10.3389/fphys.2021.752144

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Abstract

Endurance exercise induces an increase in the expression of exercise-induced peptides that participate in the repair and regeneration of skeletal muscles. The present study aimed to evaluate the time course and role of exercise-induced cytokines in muscle damage and repair after a marathon race. Fifty-seven Brazilian male amateur marathon finishers, aged 30–55 years, participated in this study. The blood samples were collected 24 h before, immediately after, and 24 and 72 h after the São Paulo International Marathon. The leukogram and muscle damage markers were analyzed using routine automated methodology in the clinical laboratory. The plasma levels of the exercise-induced cytokines were determined using the Human Magnetic Bead Panel or enzyme-linked immunosorbent assays [decorin and growth differentiation factor 15 (GDF-15)]. A muscle damage was characterized by an increase in plasma myocellular proteins and immune changes (leukocytosis and neutrophilia). Running the marathon increased interleukin (IL)-6 (4-fold), IL-8 (1.5-fold), monocyte chemoattractant protein-1 (2.4-fold), tumor necrosis factor alpha (TNF-α) (1.5-fold), IL-10 (11-fold), decorin (1.9-fold), GDF-15 (1.8-fold), brain-derived neurotrophic factor (BDNF) (2.7-fold), follistatin (2-fold), and fibroblast growth factor (FGF-21) (3.4-fold) plasma levels. We also observed a reduction in musclin, myostatin, IL-15, and apelin levels immediately after the race (by 22–36%), 24 h (by 26–52%), and 72 h after the race (by 25–53%). The changes in BDNF levels were negatively correlated with the variations in troponin levels (r = −0.36). The variations in IL-6 concentrations were correlated with the changes in follistatin (r = 0.33) and FGF-21 (r = 0.31) levels after the race and with myostatin and irisin levels 72 h after the race. The changes in IL-8 and IL-10 levels had positive correlation with variation in musclin (p < 0.05). Regeneration of exercise-induced muscle damage involves the participation of classical inflammatory mediators, as well as GDF-15, BDNF, follistatin, decorin, and FGF-21, whose functions include myogenesis, mytophagia, satellite cell activation, and downregulation of protein degradation. The skeletal muscle damage markers were not associated to myokines response. However, BDNF had a negative correlation with a myocardial damage marker. The classical anti-inflammatory mediators (IL-10, IL-8, and IL-6) induced by exercise are associated to myokines response immediately after the race and in the recovery period and may affect the dynamics of muscle tissue repair.

Highlights

The mechanical and metabolic stress, induced by the repetitive contractions of muscle fibers, causes a disruption of the sarcolemma and extracellular matrix, swelling of mitochondria, dilation of the transverse tubule system, and fragmentation of the sarcoplasmic reticulum, thereby promoting the increased permeability of the membrane and efflux of myocellular proteins into the blood circulation (Peake et al, 2017; Hody et al, 2019)
The classical anti-inflammatory mediators induced by exercise (IL-6 and IL-10) and IL-8 seem to be associated with myokines that affect the muscle repair
IL-10 and IL-8 response was associated with the musclin response, while IL-6 response was positively correlated with the fibroblast growth factor (FGF)-21 and follistatin response after the race and with myostatin, apelin, and irisin response in the recovery period

Summary

Introduction

The mechanical and metabolic stress (mitochondrial dysfunction and challenge by energy ADP/ATP ratio), induced by the repetitive contractions of muscle fibers, causes a disruption of the sarcolemma and extracellular matrix, swelling of mitochondria, dilation of the transverse tubule system, and fragmentation of the sarcoplasmic reticulum, thereby promoting the increased permeability of the membrane and efflux of myocellular proteins into the blood circulation (Peake et al, 2017; Hody et al, 2019). Despite the identification of hundreds of myokines, biological function has only been described in a small portion of myokines Many of these myokines have paracrine biological functions in muscle protein synthesis or degradation, proliferation and differentiation of myoblasts, activation of satellite cells, organization and remodeling of the extracellular matrix, as well as modulation of muscle wasting, repair, and regeneration (Hoffmann and Weigert, 2017; Lee and Jun, 2019; Laurens et al, 2020). The myokines primarily studied after aerobic exercise include myostatin, IL-6, irisin, IL-15, growth differentiation factor 15 (GDF-15), brain-derived neurotrophic factor (BDNF), fibroblast growth factor (FGF)-21, apelin, angiopoietin-like protein 4, and decorin (Safdar and Tarnopolsky, 2018; Piccirillo, 2019; Bay and Pedersen, 2020; Laurens et al, 2020). The release of exercise-induced peptides is dependent on the type of exercise and training protocol (Piccirillo, 2019; Domin et al, 2021)

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