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

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.

Exercise Induced-Cytokines Response in Marathon Runners: Role of ACE I/D and BDKRB2 +9/-9 Polymorphisms

“…Previous study of our group demonstrated a reduction of myostatin 3 days after the race which may contribute to muscle repair after exercise and a decrease of apelin and musclin in the same period (de Sousa et al, 2021). The role of these changes on muscle repair remains unclear and should be investigated.…”

“…Exercise-induced cytokines may be released by myocytes, satellite cells, endothelial cells, hepatocytes, residential macrophages, and fibroblasts, affecting skeletal and cardiac muscle as well as blood vessels, adipose tissue and brain (Hoffmann and Weigert, 2017;Lee and Jun, 2019;Laurens et al, 2020). Recently, our group demonstrated the increase of brain-derived neurotrophic factor (BDNF), fibroblast growth factor 21 (FGF-21), follistatin (FSTL) and decorin, as well as a decrease of myostatin, musclin and apelin after the race (de Sousa et al, 2021).…”

Attenuated inflammatory profile following single and repeated handgrip exercise and remote ischemic preconditioning in patients with cerebral small vessel disease

“…This suggests an altered FGF-21 signaling during cardiovascular disease, which might also occur in sCVD patients. Studies examining the acute effects of exercise on FGF-21 have presented conflicting results, ranging from an increase of FGF-21 following whole-body exercise in healthy individuals ( de Sousa et al, 2021 ; Domin et al, 2021 ; Jurimae et al, 2021 ), small FGF-21 changes in obese subjects and even lower FGF-21 in older men ( Taniguchi et al, 2016 ; Khalafi et al, 2021 ). The local handgrip exercise bout performed in our study makes it difficult to compare our results with these previous studies that have typically adopted whole-body exercise.…”

When should I run—the role of exercise timing in metabolic health

“…Very likely, production of myokines in skeletal muscle follows a diurnal rhythm 63 . Moreover, exercise‐induced release of myokines such as IL‐6 is highest immediately after exercise and levels off in the subsequent 72 h 64 . Currently, it is unknown if this timed release of mykokines depends on the time of day when exercise is performed.…”