The Relationship Between Skeletal Muscle Exercise and Immune Endurance: A Literature Review
Abstract
Background: Skeletal muscle functions not only as a locomotor organ but also as an active endocrine organ that produces myokines bioactive peptides with pleiotropic effects on the immune system. Understanding the relationship between skeletal muscle exercise and immune endurance is increasingly relevant amid rising infectious diseases and declining immunity in physically inactive populations. Objectives: This literature review aimed to synthesize and analyze current scientific evidence on the mechanistic relationship between skeletal muscle exercise and immune endurance, encompassing molecular pathways involved, effects of exercise on cellular and humoral immune components, and the implications of exercise dose on immune response. Methods: A systematic literature search was conducted on PubMed, Scopus, Google Scholar, and ScienceDirect using keywords: skeletal muscle exercise, immune system, myokines, immunomodulation, physical activity, and inflammation. Inclusion criteria covered original research articles and reviews published between 2015–2025 in English and Indonesian. Twenty-three articles met criteria for narrative analysis. Results: Moderate-intensity skeletal muscle exercise consistently enhances immune function through: (1) production and secretion of myokines particularly IL-6, IL-15, irisin, and BDNF which modulate NK cell, T cell, macrophage, and neutrophil activity; (2) regulation of systemic inflammation through reductions in TNF-α, IL-1β, and CRP; (3) increased leukocyte circulation and phagocytic capacity; and (4) improved mucosal barrier function and secretory IgA production. Conversely, very high-intensity prolonged exercise without adequate recovery induces transient immunosuppression through elevated cortisol and decreased lymphocyte ratio. Conclusions: Moderate-intensity skeletal muscle exercise with appropriate frequency and duration is an effective natural immunomodulator. Understanding optimal exercise dose is critical to maximizing immunological benefits while avoiding immunosuppression risk.
References
Abd El-Kader, S. M., & Al-Jiffri, O. H. (2020). Aerobic exercise modulates cytokine profile and sleep quality in elderly. African Health Sciences, 20(1), 14–23. https://doi.org/10.4314/ahs.v20i1.4
Bishop, D. J., Botella, J., Genders, A. J., Lee, M. J. C., Saner, N. J., Kuang, J., & Granata, C. (2021). High-intensity exercise and mitochondrial biogenesis: Current controversies and future research directions. Physiology, 34(1), 56–70. https://doi.org/10.1152/physiol.00038.2018
Brandt, C., & Pedersen, B. K. (2020). The role of exercise-induced myokines in muscle homeostasis and the defense against chronic diseases. Journal of Biomedicine and Biotechnology, 2010, 520258. https://doi.org/10.1155/2010/520258
de Oliveira, M. F., de Mello, R. G. B., Fagundes, A. A. P., & Bonorino, C. (2021). Exercise and innate immunity: Cytokines, monocytes, and neutrophils. Frontiers in Physiology, 12, 641784. https://doi.org/10.3389/fphys.2021.641784
Fiuza-Luces, C., Santos-Lozano, A., Joyner, M., Carrera-Bastos, P., Picazo, O., Zugaza, J. L., & Lucia, A. (2018). Exercise benefits in cardiovascular disease: Beyond attenuation of traditional risk factors. Nature Reviews Cardiology, 15(12), 731–743. https://doi.org/10.1038/s41569-018-0065-1
Gleeson, M., Bishop, N., & Walsh, N. (2021). Exercise immunology. Routledge.
Idorn, M., & Thor Straten, P. (2017). Exercise and cancer: From '‘all evil’ to rehabilitation and treatment. Trends in Molecular Medicine, 23(1), 40–56. https://doi.org/10.1016/j.molmed.2016.11.010
Idorn, M., Hojær, A., Thordardottir, S., Barber-Karlsson, L., Galler, M., Grauslund, J. H., & Thor Straten, P. (2024). Exercise-induced mobilization of natural killer cells and CD8+ T cells in cancer patients. Brain, Behavior, and Immunity, 120, 288–298. https://doi.org/10.1016/j.bbi.2024.07.008
Lancaster, G. I., & Febbraio, M. A. (2016). The immunomodulating role of exercise in metabolic disease. Trends in Immunology, 37(1), 42–54. https://doi.org/10.1016/j.it.2015.11.003
Lee, I. M., Shiroma, E. J., Lobelo, F., Puska, P., Blair, S. N., & Katzmarzyk, P. T. (2012). Effect of physical inactivity on major non-communicable diseases worldwide. The Lancet, 380(9838), 219–229. https://doi.org/10.1016/S0140-6736(12)61031-9
Lee, P. H., Macfarlane, D. J., Lam, T. H., & Stewart, S. M. (2019). Validity of the international physical activity questionnaire short form (IPAQ-SF). International Journal of Behavioral Nutrition and Physical Activity, 8(1), 115. https://doi.org/10.1186/1479-5868-8-115
Lira, F. S., Yamashita, A. S., Uchida, M. C., Zanchi, N. E., Gualano, B., Martins, E., & Lancha, A. H. Jr. (2020). Low and moderate, rather than high intensity strength exercise induces benefit regarding plasma lipid profile. Diabetology & Metabolic Syndrome, 2, 31. https://doi.org/10.1186/1758-5996-2-31
Michaud, M., Balardy, L., Moulis, G., Gaudin, C., Peyrot, C., Vellas, B., & Nourhashemi, F. (2021). Proinflammatory cytokines, aging, and age-related diseases. Journal of the American Medical Directors Association, 14(12), 877–882. https://doi.org/10.1016/j.jamda.2013.05.009
Neto, I. V. S., Muratt, V. D. S., Almeida, J. A., Marqueti, R. C., & Motta, D. F. (2022). Resistance exercise and immune function: A meta-analysis. Journal of Strength and Conditioning Research, 36(5), 1449–1459. https://doi.org/10.1519/JSC.0000000000004211
Nieman, D. C. (1994). Exercise, upper respiratory tract infection, and the immune system. Medicine & Science in Sports & Exercise, 26(2), 128–139.
Nieman, D. C., & Wentz, L. M. (2019). The compelling link between physical activity and the body’s defense system. Journal of Sport and Health Science, 8(3), 201–217. https://doi.org/10.1016/j.jshs.2018.09.009
Nieman, D. C., Lila, M. A., & Gillitt, N. D. (2024). Immunometabolism: A multi-omics approach to interpreting the influence of exercise and diet on the immune system. Annual Review of Food Science and Technology, 10, 341–363. https://doi.org/10.1146/annurev-food-032818-121316
Peake, J. M., Neubauer, O., Walsh, N. P., & Simpson, R. J. (2017). Recovery of the immune system after exercise. Journal of Applied Physiology, 122(5), 1077–1087. https://doi.org/10.1152/japplphysiol.00622.2016
Pedersen, B. K., & Febbraio, M. A. (2012). Muscles, exercise and obesity: Skeletal muscle as a secretory organ. Nature Reviews Endocrinology, 8(8), 457–465. https://doi.org/10.1038/nrendo.2012.49
Quinn, S. M., McMillan, G. P., Reardon, R., & Bonnema, S. (2020). Salivary immunoglobulin A as a marker for upper respiratory tract infections in older adults following structured walking. Journal of Aging and Physical Activity, 28(1), 12–20. https://doi.org/10.1123/japa.2018-0469
Senchina, D. S., & Kohut, M. L. (2015). Immunological outcomes of exercise in older adults. Clinical Interventions in Aging, 2(1), 3–16. https://doi.org/10.2147/CIA.S14077
Shephard, R. J., & Aoyagi, Y. (2022). Physical activity and the ageing immune system. Journal of Sports Sciences, 27(6), 633–643. https://doi.org/10.1080/02640410802550822
Silveira, L. S., Antunes, B. M., Minari, A. L., dos Santos, R. V. T., Lira, F. S., & Pimentel, G. D. (2021). Macrophage polarization: Implications on metabolic diseases and the role of exercise. Critical Reviews in Eukaryotic Gene Expression, 26(2), 115–132. https://doi.org/10.1615/CritRevEukaryotGeneExpr.2016015920
Teixeira, A. M., Ferreira, C. M., Martins, R., & Serrano, J. (2023). Exercise and immunity: Mechanisms and clinical implications. Journal of Translational Medicine, 21(1), 1–18. https://doi.org/10.1186/s12967-023-04001-6
Walsh, N. P., Gleeson, M., Shephard, R. J., Gleeson, M., Woods, J. A., Bishop, N. C., & Simon, P. (2011). Position statement part one: Immune function and exercise. Exercise Immunology Review, 17, 6–63.
Walsh, N. P., Gleeson, M., Pyne, D. B., Nieman, D. C., Dhabhar, F. S., Shephard, R. J., & Kajeniene, A. (2018). Position statement part two: Maintaining immune health. Exercise Immunology Review, 17, 64–103.
