Endurance training enhances skeletal muscle interleukin-15 in human male subjects
Abstract
Regular endurance exercise promotes metabolic and oxidative changes in skeletal muscle. Overexpression of interleukin-15 (IL-15) in mice exerts similar metabolic changes in muscle as seen with endurance exercise. Muscular IL-15 production has been shown to increase in mice after weeks of regular endurance running. With the present study we aimed to determine if muscular IL-15 production would increase in human male subjects following 12 weeks of endurance training. In two different studies we obtained plasma and muscle biopsies from young healthy subjects performing: (1) 12 weeks of ergometer cycling exercise five times per week with plasma and biopsies before and after the intervention, and (2) 3 h of ergometer cycling exercise with plasma and biopsies before and after the exercise bout and well into recovery. We measured changes in plasma IL-15, muscle IL-15 mRNA and IL-15 protein. Twelve weeks of regular endurance training induced a 40% increase in basal skeletal muscle IL-15 protein content (p < 0.01), but with no changes in either muscle IL-15 mRNA or plasma IL-15 levels. However, an acute bout of 3-h exercise did not show significant changes in muscle IL-15 or plasma IL-15 levels. The induction of muscle IL-15 protein in humans following a regular training period supports previous findings in mice and emphasizes the hypothesis of IL-15 taking part in skeletal muscle adaptation during training.
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IL-15 concentrations in skeletal muscle biopsies are markedly increased despite no apparent increase in the circulation following exercise.
“IL-15 concentrations in SkM biopsies are markedly increased despite no apparent increase in the circulation following exercise [85].”
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“To our knowledge, the models previous studies used mainly focused on human and rat (Yang et al., 2013; Molanouri Shamsi et al., 2014; Rinnov et al., 2014), and not a single study has considered the dynamic changes of IL-15 expression at each level in suckling piglets and in weaning piglets.”
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Role of Protein Arginine Methyltransferases and Inflammation in Muscle Pathophysiology
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Farley, M. J., Bartlett, D. B., Skinner, T. L., Schaumberg, M. A., & Jenkins, D. G. (2022) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000003067 · Cited by 22 · see citing works
“…RT: Hingorjo et al. (2018) (47) M and F 133 obese and nonobese (18.37 ± 0.63) Serum IL-15 AT: (3 Pierce et al. (2015) (42) M and F 20 lean/obese Plasma IL-15 AT: Rinnov et al. (2014) (45) M 15 healthy (27.0 ± 3.7) Plasma IL-15 AT: Christiansen et al. (2013) (94) M and F 31 overweight/lean…”
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“In both active and inactive individuals, no changes in resting circulating levels of IL-15 have been observed following any chronic exercise programs (Nieman et al. 2003, Riechman et al. 2004, Rinnov et al. 2014).”
BackgroundMalczynska-Sims, P., Chalimoniuk, M., & Sułek, A. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.578981 · Cited by 17 · see citing works
Farley, M. J., Boytar, A. N., Adlard, K. N., Salisbury, C. E., Hart, N. H., Schaumberg, M. A., Jenkins, D. G., & Skinner, T. L. (2024) · The Journal of Physiology · doi:10.1113/jp286043 · Cited by 18 · see citing works
“Of the two studies (He et al., 2018; Rinnov et al., 2014) that did not observe a significant effect of exercise on IL-15 concentrations, both included young healthy populations and did not report baseline concentrations of IL-15, which may have influenced the response to exercise.”
Antioxidants Facilitate High–intensity Exercise IL–15 Expression in Skeletal Muscle
Pérez‐López, A., Martín-Rincón, M., Santana, A., Pérez-Suárez, I., Dorado, C., Calbet, J. A. L., & Morales‐Álamo, D. (2018) · International Journal of Sports Medicine · doi:10.1055/a-0781-2527 · Cited by 17 · see citing works
“In humans, exercise-induced skeletal muscle IL-15 expression has been suggested to be stimulated in an intensity-dependent manner [27]; however, the IL-15 response to high-intensity exercise has not been previously investigated.”
BackgroundMethodAnti-inflammatory effects of exercise training. A systematic review
Onu, I., Iordan, D. A., Codreanu, C. M., Daniela, M., & Galaction, A. (2021) · Balneo and PRM Research Journal · doi:10.12680/balneo.2021.473 · Cited by 17 · see citing works
“L-15 L-15 is an anabolic factor present in the muscle, and high expression of IL-15 prevents increasing of visceral fat, and its related to reduced WAT mass. IL-15 IL-15 has been shown to be increased in trained human muscle (75-78).”
BackgroundRole of Distinct Fat Depots in Metabolic Regulation and Pathological Implications
Sahu, B., Tikoo, O., Pati, B., Senapati, U., & Bal, N. C. (2022) · Reviews of physiology, biochemistry and pharmacology · doi:10.1007/112_2022_73 · Cited by 15 · see citing works
Potential Biomarkers for Physical Exercise-Induced Brain Health
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Role of Biomarkers in Medicine
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Hormonal, immune, and oxidative stress responses to blood flow‐restricted exercise
Hjortshoej, M. H., Aagaard, P., Storgaard, C. D., Juneja, H., Lundbye‐Jensen, J., Magnusson, S. P., & Couppé, C. (2023) · Acta Physiologica · doi:10.1111/apha.14030 · Cited by 13 · see citing works
Immunological mechanisms of exercise therapy in dyslipidemia
Krüger, K., Tirekoglou, P., & Weyh, C. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.903713 · Cited by 13 · see citing works
“IL-15 appears to have effects on the induction of better survival of naïve T cells.”
BackgroundInfluentialBodnaruc, A. M., Roberge, M., Giroux, I., & Aguer, C. (2024) · Endocrines · doi:10.3390/endocrines5040035 · Cited by 12 · see citing works
“Interestingly, a 12-week endurance training study conducted in men has shown an increase in the expression of muscular IL-15 following endurance training [201], potentially contributing to decreasing visceral fats and subsequent inflammation.”
Thyroid hormones regulate skeletal muscle regeneration after acute injury
Leal, A. L. R. C., Cavalcanti‐de‐Albuquerque, J. P., Matos, M. S., Fortunato, R. S., de Carvalho, D. P., Rosenthal, D., & da Costa, V. M. C. (2014) · Endocrine · doi:10.1007/s12020-014-0271-5 · Cited by 9 · see citing works
“Regular endurance exercise enhances skeletal muscle interleukin-15-mediating muscle adaptation during training [28].”
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“Previous studies on the effects of exercise on IL-15 in skeletal muscle and content of IL-15 in plasma were inconsistent (16).”
Background10 km running race induces an elevation in the plasma myokine level of nonprofessional runners
Marcucci-Barbosa, L. S., Júnior, F. D. A. D. M., Lobo, L. F., Morais, M. G., Moreira, J. M., Vieira, É. L. M., & Nunes-Silva, A. (2019) · Sport Sciences for Health · doi:10.1007/s11332-019-00608-3 · Cited by 7 · see citing works
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“Actually, it is discussed if the effect of exercise training protects against abdominal adiposity is mediated by IL-15 [59].”
Jakobsson, J., Cotgreave, I. A., Furberg, M., Arnberg, N., & Svensson, M. (2021) · Sports · doi:10.3390/sports9090121 · Cited by 6 · see citing works
“IL-15 is also essential for maintaining memory CD8+ T cells [187] and NK-cell activation, production, and cytotoxicity [188], making it an important factor in the stimulation of immune responses to infections.”
BackgroundMyokines: A central point in managing redox homeostasis and quality of life
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Muscle–immune metabolic crosstalk: shared pathways in cachexia and exercise
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The impact of dietary intervention on myokines: a narrative review
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“Their release is influenced by exercise intensity, duration, and muscle mass (Wärnberg et al. 2010; Rinnov et al. 2014; Schnyder and Handschin 2015).”
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Two‐Way Communication Between Skeletal Muscle and Myokines
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IL-15 : A NOVEL REGULATOR OF LIPOLYSIS IN HUMANS?
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- Authors
- Rinnov, A., Yfanti, C., Nielsen, S., Åkerström, T. C. A., Peijs, L., Zankari, A., Fischer, C. P., & Pedersen, B. K.
- Affiliations
- University of Copenhagen (DK)
- Corresponding author
- Rinnov, Anders
- Venue
- Endocrine
- Published
- 2013-05-07
- Volume
- 45
- Issue
- 2
- Pages
- 271-278
- ISSN
- 0969-711X (ISSN-L)
- 1355-008X
- 1559-0100
- OpenAlex
- W2020374367
- Cited by
- 103
- References
- 32
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 10 · 2023: 5 · 2022: 14 · 2021: 12 · 2020: 11 · 2019: 6 · 2018: 10 · 2017: 4 · 2016: 9 · 2015: 8 · 2014: 6
- FWCI
- 8.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Endocrine (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Keywords
- IL-15, endurance training, skeletal muscle, muscle adaptation, acute exercise, cycle ergometry, plasma cytokines, exercise training
- MeSH terms
- Adaptation, Physiological, Adult, Biopsy, Exercise Test, Humans, Male, Physical Endurance, RNA, Messenger, Time Factors, Exercise, Up-Regulation, Muscle, Skeletal, Interleukin-15
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