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

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.

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Marathon Race Affects Neutrophil Surface Molecules: Role of Inflammatory Mediators

PLoS ONE ◽

10.1371/journal.pone.0166687 ◽

2016 ◽

Vol 11 (12) ◽

pp. e0166687 ◽

Cited By ~ 10

Author(s):

Vinicius Coneglian Santos ◽

Ana Paula Renno Sierra ◽

Rodrigo Oliveira ◽

Kim Guimarães Caçula ◽

César Miguel Momesso ◽

...

Keyword(s):

Inflammatory Mediators ◽

Surface Molecules ◽

Marathon Race ◽

Neutrophil Surface

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Muscle damage and inflammation during recovery from exercise

Journal of Applied Physiology ◽

10.1152/japplphysiol.00971.2016 ◽

2017 ◽

Vol 122 (3) ◽

pp. 559-570 ◽

Cited By ~ 132

Author(s):

Jonathan M. Peake ◽

Oliver Neubauer ◽

Paul A. Della Gatta ◽

Kazunori Nosaka

Keyword(s):

Muscle Strength ◽

Muscle Damage ◽

Muscle Tissue ◽

Time Course ◽

Inflammatory Responses ◽

Large Body ◽

Clinical Signs ◽

Muscle Length ◽

Signs And Symptoms ◽

Exercise Induced

Unaccustomed exercise consisting of eccentric (i.e., lengthening) muscle contractions often results in muscle damage characterized by ultrastructural alterations in muscle tissue, clinical signs, and symptoms (e.g., reduced muscle strength and range of motion, increased muscle soreness and swelling, efflux of myocellular proteins). The time course of recovery following exercise-induced muscle damage depends on the extent of initial muscle damage, which in turn is influenced by the intensity and duration of exercise, joint angle/muscle length, and muscle groups used during exercise. The effects of these factors on muscle strength, soreness, and swelling are well characterized. By contrast, much less is known about how they affect intramuscular inflammation and molecular aspects of muscle adaptation/remodeling. Although inflammation has historically been viewed as detrimental for recovery from exercise, it is now generally accepted that inflammatory responses, if tightly regulated, are integral to muscle repair and regeneration. Animal studies have revealed that various cell types, including neutrophils, macrophages, mast cells, eosinophils, CD8 and T-regulatory lymphocytes, fibro-adipogenic progenitors, and pericytes help to facilitate muscle tissue regeneration. However, more research is required to determine whether these cells respond to exercise-induced muscle damage. A large body of research has investigated the efficacy of physicotherapeutic, pharmacological, and nutritional interventions for reducing the signs and symptoms of exercise-induced muscle damage, with mixed results. More research is needed to examine if/how these treatments influence inflammation and muscle remodeling during recovery from exercise.

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Exercise-induced satellite cell activation in growing and mature skeletal muscle

Journal of Applied Physiology ◽

10.1152/jappl.1987.63.5.1816 ◽

1987 ◽

Vol 63 (5) ◽

pp. 1816-1821 ◽

Cited By ~ 153

Author(s):

K. C. Darr ◽

E. Schultz

Keyword(s):

Satellite Cell ◽

Cross Sections ◽

Time Course ◽

Cell Activation ◽

Treadmill Running ◽

Rapid Decline ◽

Fiber Damage ◽

Single Bout ◽

Satellite Cell Activation ◽

Exercise Induced

The time course and extent of satellite cell activation were studied in the soleus (m-SOL) and extensor digitorum longus (m-EDL) muscles of untrained growing and mature rats after a single bout of prolonged eccentric treadmill running. At 24, 48, 72, and 120 h postexercise, satellite cell mitotic activity was quantitated in autoradiographs of whole-fiber segments after injection of [3H]thymidine. Fiber damage and localization of labeled cells were also examined in muscle cross sections. Labeling in growing muscles progressively increased to peak levels (approximately 250% of control) at 72 h postexercise, whereas mature muscles exhibited an earlier peak (approximately 250% of control) at 24 (m-SOL) and 48 (m-EDL) h, followed by a more rapid decline to control levels by 120 h postexercise. In all exercised muscles the calculated satellite cell activation was far greater than required to repair the small number (less than 3.0%) of necrotic fibers identified at the light-microscopic level. These results suggest that satellite cells were activated not only on fibers exhibiting overt necrosis but also on those with lesions not discernible with light microscopy.

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Time Course of Change in Critical Torque following Exercise-Induced Muscle Damage

Medicine & Science in Sports & Exercise ◽

10.1249/01.mss.0000563201.19473.2f ◽

2019 ◽

Vol 51 (Supplement) ◽

pp. 902

Author(s):

Robert E. Hight ◽

Darshit S. Patel ◽

Jessica A. Peterson ◽

Cameron Lohman ◽

Jason A. Campbell ◽

...

Keyword(s):

Muscle Damage ◽

Time Course ◽

Exercise Induced

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Influence of different types of compression garments on exercise-induced muscle damage markers after a soccer match

Research in Sports Medicine ◽

10.1080/15438627.2017.1393755 ◽

2017 ◽

Vol 26 (1) ◽

pp. 27-42 ◽

Cited By ~ 5

Author(s):

Diego Marqués-Jiménez ◽

Julio Calleja-González ◽

Iñaki Arratibel-Imaz ◽

Anne Delextrat ◽

Fernando Uriarte ◽

...

Keyword(s):

Muscle Damage ◽

Compression Garments ◽

Soccer Match ◽

Different Types ◽

Exercise Induced ◽

Muscle Damage Markers

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The repeated bout effect of traditional resistance exercises on running performance across 3 bouts

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2017-0214 ◽

2017 ◽

Vol 42 (9) ◽

pp. 978-985 ◽

Cited By ~ 10

Author(s):

Kenji Doma ◽

Moritz Schumann ◽

Anthony Scott Leicht ◽

Brian Edward Heilbronn ◽

Felipe Damas ◽

...

Keyword(s):

Resistance Training ◽

Muscle Damage ◽

Muscle Soreness ◽

Recovery Period ◽

Repeated Bout Effect ◽

Lower Body ◽

Running Performance ◽

The Third ◽

Repeated Bout ◽

Muscle Damage Markers

This study investigated the repeated bout effect of 3 typical lower body resistance-training sessions on maximal and submaximal effort running performance. Twelve resistance-untrained men (age, 24 ± 4 years; height, 1.81 ± 0.10 m; body mass, 79.3 ± 10.9 kg; peak oxygen uptake, 48.2 ± 6.5 mL·kg−1·min−1; 6-repetition maximum squat, 71.7 ± 12.2 kg) undertook 3 bouts of resistance-training sessions at 6-repetitions maximum. Countermovement jump (CMJ), lower-body range of motion (ROM), muscle soreness, and creatine kinase (CK) were examined prior to and immediately, 24 h (T24), and 48 h (T48) after each resistance-training bout. Submaximal (i.e., below anaerobic threshold (AT)) and maximal (i.e., above AT) running performances were also conducted at T24 and T48. Most indirect muscle damage markers (i.e., CMJ, ROM, and muscle soreness) and submaximal running performance were significantly improved (P < 0.05; 1.9%) following the third resistance-training bout compared with the second bout. Whilst maximal running performance was also improved following the third bout (P < 0.05; 9.8%) compared with other bouts, the measures were still reduced by 12%–20% versus baseline. However, the increase in CK was attenuated following the second bout (P < 0.05) with no further protection following the third bout (P > 0.05). In conclusion, the initial bout induced the greatest change in CK; however, at least 2 bouts were required to produce protective effects on other indirect muscle damage markers and submaximal running performance measures. This suggests that submaximal running sessions should be avoided for at least 48 h after resistance training until the third bout, although a greater recovery period may be required for maximal running sessions.

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Role of brain macrophages on IL-1β and fatigue following eccentric exercise-induced muscle damage

Brain Behavior and Immunity ◽

10.1016/j.bbi.2009.12.011 ◽

2010 ◽

Vol 24 (4) ◽

pp. 564-568 ◽

Cited By ~ 29

Author(s):

Martin D. Carmichael ◽

J. Mark Davis ◽

E. Angela Murphy ◽

James A. Carson ◽

N. Van Rooijen ◽

...

Keyword(s):

Muscle Damage ◽

Eccentric Exercise ◽

Brain Macrophages ◽

Exercise Induced

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Endurance exercise causes interaction among stress hormones, cytokines, neutrophil dynamics, and muscle damage

Journal of Applied Physiology ◽

10.1152/jappl.1999.87.4.1360 ◽

1999 ◽

Vol 87 (4) ◽

pp. 1360-1367 ◽

Cited By ~ 171

Author(s):

Katsuhiko Suzuki ◽

Manabu Totsuka ◽

Shigeyuki Nakaji ◽

Mutsuo Yamada ◽

Satoru Kudoh ◽

...

Keyword(s):

Muscle Damage ◽

Stress Hormones ◽

Plasma Growth Hormone ◽

Bioactive Substances ◽

Daily Exercise ◽

Repeated Exercise ◽

Exercise Induced ◽

Neutrophil Priming ◽

Muscle Damage Markers ◽

Experimental Challenge

We analyzed adaptation mechanisms regulating systemic inflammatory response of the stressed body by using an experimental challenge of repeated exercise bouts and accompanying muscle inflammation. Eight untrained men bicycled at 90 W for 90 min, 3 days in a row. Exercise induced peripheral neutrophilia with a leftward shift of neutrophil nucleus and neutrophil priming for oxidative activity determined by luminol-dependent chemiluminescence. Plasma growth hormone and interleukin-6 rose significantly after exercise and were closely correlated with the neutrophil responses. Serum creatine kinase and myoglobin levels as muscle damage markers rose after exercise in “delayed onset” and were closely correlated with the preceding neutrophil responses. These exercise-induced responses were strongest on day 1, but the magnitude gradually decreased with progressive daily exercise. In contrast, the magnitude of catecholamine responses to exercise sessions gradually rose, possibly suppressing neutrophil oxidative responses. These results indicate that stress-induced systemic release of bioactive substances may determine neutrophil mobilization and functional status, which then may affect local tissue damage of susceptible organs.

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