Issue 24-1, 2025

Review

https://doi.org/10.38025/2078-1962-2025-24-1-91-102

Effect of Physical Activity on the Immune System in the Normal State and in Various Diseases: a Review

View article (Download PDF file)



Download XML file

1,3 ORCIDDmitry A. Vologzhanin, 3,* ORCIDAleksandr S. Golota, 3 ORCIDAnna-Maria I. Ignatenko, 3 ORCIDTatyana A. Kamilova, 2 ORCIDDenis V. Kovlen, 3Elena V. Usikova, 1,3 ORCIDSergey G. Shcherbak

1 St Petersburg University, Saint-Petersburg, Russia
2 S.M. Kirov Military Medical Academy, Saint-Petersburg, Russia
3 Municipal Hospital No. 40, Kurortny District, Saint-Petersburg, Russia


ABSTRACT

INTRODUCTION. Regular physical exercise has a beneficial effect on health, affecting all body systems and reducing morbidity. Muscle fiber activity during exercise helps reduce levels of inflammatory markers and stimulate anti-inflammatory responses. The ability to maintain homeostasis while exercising and adaptation to exercises depend on physical fitness, comorbidities and other factors, so the exercise program should be tailored to the individual.

THE MAIN CONTENT OF THE REVIEW. Immune system activation in response to exercise is mediated by cytokine signaling. The main source of cytokines during physical activity is the skeletal muscles themselves. Cytokines produced by myocytes (myokines) during muscle contraction play a key role in providing communication between working muscles and other organs and tissues. Numerous studies have shown a positive effect of moderate intensity exercise on myokine secretion. People with chronic infectious or non-infectious diseases often demonstrate low-grade systemic inflammation and low levels of circulating myokines. Moderate intensity exercise has anti-inflammatory effects in inflammatory conditions and diseases. Exercise is a popular non-pharmacological adjunct to traditional treatments and rehabilitation for many diseases.

CONCLUSION. Understanding the relationship between exercise modalities and myokine response helps to optimize treatment and rehabilitation recommendations for populations with different needs, such as patients with cancer, chronic inflammatory diseases, or post-viral infection syndromes.


KEYWORDS: exercise, inflammation, cytokine, myokine, skeletal muscle, rehabilitation, chronic inflammatory diseases

FOR CITATION:

Vologzhanin D.A., Golota A.S., Ignatenko A.-M.I., Kamilova T.A., Kovlen D.V., Usikova E.V., Shcherbak S.G. Effect of Physical Activity on the Immune System in the Normal State and in Various Diseases: a Review. Bulletin of Rehabilitation Medicine. 2025; 24(1):91–102. https://doi.org/10.38025/2078-1962-2025-24-1-91-102 (In Russ.).

FOR CORRESPONDENCE: Aleksandr S. Golota, Е-mail: golotaa@yahoo.com, b40@zdrav.spb.ru


References:

  1. Bull F.C., Al-Ansari S.S., Biddle S. et al. World Health Organization 2020 guidelines on physical activity and sedentary behaviour. Br J Sports Med. 2020; 54(24): 1451–1462. https://doi.org/10.1136/bjsports-2020-102955
  2. MoTrPAC Study Group, Lead Analysts, MoTrPAC Study Group. Temporal dynamics of the multi-omic response to endurance exercise training. Nature. 2024; 629(8010): 174–183. https://doi.org/10.1038/s41586-023-06877-w
  3. Sato S., Dyar K.A., Treebak J.T. et al. Atlas of exercise metabolism reveals time-dependent signatures of metabolic homeostasis. Cell Metab. 2022; 34(2): 329–345.e8. https://doi.org/10.1016/j.cmet.2021.12.016
  4. MacIntosh B.R., Murias J.M., Keir D.A. et al. What Is Moderate to Vigorous Exercise Intensity? Front Physiol. 2021; 12: 682233. https://doi.org/10.3389/fphys.2021.682233
  5. Docherty S., Harley R., McAuley J.J. et al. The effect of exercise on cytokines: Implications for musculoskeletal health: A narrative review. BMC Sports Sci Med Rehabil 2022; 14(1): 5. https://doi.org/10.1186/s13102-022-00397-2
  6. Garneau L., Mulvihill E.E., Smith S.R. et al. Myokine Secretion following an Aerobic Exercise Intervention in Individuals with Type 2 Diabetes with or without Exercise Resistance. Int J Mol Sci. 2024; 25(9): 4889. https://doi.org/10.3390/ijms25094889
  7. Severinsen M.C.K., Pedersen B.K. Muscle-organ crosstalk:the emerging roles of myokines. Endocr Rev. 2020; 41(4): 594–609. https://doi.org/10.1210/endrev/bnaa016
  8. Fiuza-Luces C., Valenzuela P.L., Gálvez B.G. et al. The effect of physical exercise on anticancer immunity. Nat Rev Immunol. 2024; 24(4): 282–293. https://doi.org/10.1038/s41577-023-00943-0
  9. Ringleb M., Javelle F., Haunhorst S. et al. Beyond muscles:Investigating immunoregulatory myokines in acute resistance exercise – A systematic review and meta-analysis. FASEB J. 2024; 38(7): e23596. https://doi.org/10.1096/fj.202301619R
  10. Kistner T.M., Pedersen B.K., Lieberman D.E. Interleukin 6 as an energy allocator in muscle tissue. Nat Metab. 2022; 4(2): 170–179. https://doi.org/10.1038/s42255-022-00538-4
  11. Arazi H., Falahati A., Suzuki K. Moderate intensity aerobic exercise potential favorable effect against COVID-19: the role of renin-angiotensin system and immunomodulatory effects. Front Physiol. 2021; 12: 747200. https://doi.org/10.3389/fphys.2021.747200
  12. Do Brito Valente A.F., Jaspers R.T., Wüst R.C. Regular physical exercise mediates the immune response in atherosclerosis. Exerc Immunol Rev. 2021; 27: 42–53.
  13. Kramer A. An overview of the beneficial effects of exercise on health and performance. Adv Exp Med Biol. 2020; 1228: 3–22. https://doi.org/10.1007/978-981-15-1792-1_1
  14. Marcucci-Barbosa L., Martins-Junior F., Lobo L. et al. The effects of strength training session with different types of muscle action on white blood cells counting and Th1/Th2 response. Sport Sciences for Health. 2020; 16: 239–248. https://doi.org/10.1007/s11332-019-00597-3
  15. Islam H., Neudorf H., Mui A. et al. Interpreting ‘anti-inflammatory’ cytokine responses to exercise:focus on interleukin-10. J Physiol. 2021; 599(23): 5163–5177. https://doi.org/10.1113/JP281356
  16. Fonseca H.A.R., Bittencourt C.R., Monteiro A.M. et al. Immunometabolic and vascular health responses among high endurance trained subjects. Int J Sports Med. 2024; 45(3): 245–252. https://doi.org/10.1055/a-2186-2717
  17. Knudsen N.H., Stanya K.J., Hyde A.L. et al. Interleukin-13 drives metabolic conditioning of muscle to endurance exercise. Science. 2020; 368(6490): eaat3987. https://doi.org/10.1126/science.aat3987
  18. Cheng A.J., Jude B., Lanner J.T. Intramuscular mechanisms of overtraining. Redox Biol. 2020; 35: 101480. https://doi.org/10.1016/j.redox.2020.101480
  19. Morais G.P., Chemerka C., Masson A. et al. Excessive downhill training leads to early onset of knee osteoarthritis. Osteoarthr Cartil. 2021; 29(6): 870–881. https://doi.org/10.1016/j.joca.2021.03.016
  20. Korb A., Bertoldi K., Lovatel G.A. et al. Acute exercise and periodized training in different environments affect histone deacetylase activity and interleukin-10 levels in peripheral blood of patients with type 2 diabetes. Diabetes Res. Clin. Pract. 2018; 141: 132–139. https://doi.org/10.1016/j.diabres.2018.04.037
  21. García-Hermoso A., Ramírez-Vélez R., Díez J González A. et al. Exercise training-induced changes in exerkine concentrations may be relevant to the metabolic control of type 2 diabetes mellitus patients: A systematic review and meta-analysis of randomized controlled trials. J. Sport Health Sci. 2023; 12(2): 147–157. https://doi.org/10.1016/j.jshs.2022.11.003
  22. Garneau L., Parsons S.A., Smith S.R. et al. Plasma myokine concentrations after acute exercise in non-obese and obese sedentary women. Front Physiol. 2020; 11: 18. https://doi.org/10.3389/fphys.2020.00018
  23. Tarigan A.P., Firdaus R., Pandia P. et al. Effectiveness of upper arm and breathing exercises to improve inflammatory markers in severe COVID-19 patients. Narra J. 2024; 4(1): e417. https://doi.org/10.52225/narra.v4i1.417
  24. Rebello C.J., Axelrod C.L., Reynolds C.F. 3rd et al. Exercise as a Moderator of Persistent Neuroendocrine Symptoms of COVID-19. Exerc Sport Sci Rev. 2022; 50(2): 65–72. https://doi.org/10.1249/JES.0000000000000284
  25. Filgueira T.O., Carvalho P.R.C., de Sousa Fernandes M.S. et al. The impact of supervised physical exercise on chemokines and cytokines in recovered COVID-19 patients. Front Immunol. 2023; 13: 1051059. https://doi.org/10.3389/fimmu.2022.1051059
  26. Tortella P., D'elia F., Coco D. et al. Effect of physical activity on COVID-19 symptoms: A narrative review. J Hum Sport Exerc. 2021; 16: S2042–S2056.
  27. Steenkamp L., Saggers R.T., Bandini R. et al. Small steps, strong shield: directly measured, moderate physical activity in 65 361 adults is associated with significant protective effects from severe COVID-19 outcomes. Br J Sports Med. 2022; 56(10): 568–576. https://doi.org/10.1136/bjsports-2021-105159
  28. Sobhy E., Kamal M.M., Saad Y. et al. Effect of branched-chain amino acid supplementation and exercise on quadriceps muscle quantity and quality in patients with cirrhosis as assessed by ultrasonography: A randomized controlled trial. Clin Nutr ESPEN. 2024; 61: 108–118. https://doi.org/10.1016/j.clnesp.2024.03.011
  29. Minniti G., Pescinini-Salzedas L.M., Minniti G.A.D.S. et al. Organokines, sarcopenia, and metabolic repercussions:the vicious cycle and the interplay with exercise. Int J Mol Sci. 2022; 23(21): 13452. https://doi.org/10.3390/ijms232113452
  30. Piętowska Z., Nowicka D., Szepietowski J. Can biological drugs diminish the risk of sarcopenia in psoriatic patients? A systematic review. Life. 2022; 12(3): 435. https://doi.org/10.3390/life12030435
  31. Jung H.N., Jung C.H., Hwang Y.C. Sarcopenia in youth. Metabolism. 2023; 144: 155557. https://doi.org/10.1016/j.metabol.2023.155557
  32. Hu J., Wang Y., Ji X. et al. Non-pharmacological strategies for managing sarcopenia in chronic diseases. Clin Interv Aging. 2024; 19: 827–841. https://doi.org/10.2147/CIA.S455736
  33. Supriya R., Singh K.P., Gao Y. et al. Effect of exercise on secondary sarcopenia:a comprehensive literature review. Biology. 2021; 11(1): 51. https://doi.org/10.3390/biology11010051
  34. Cui H., Wang Z., Wu J. et al. Geriatrics Branch of the Chinese Medical Association. Chinese expert consensus on prevention and intervention for elderly with sarcopenia (2023). AGING Med. 2023; 6(2): 104–115. https://doi.org/10.1002/agm2.12245
  35. Park J., Bae J., Lee J. Complex exercise improves anti-inflammatory and anabolic effects in osteoarthritis-induced sarcopenia in elderly women. Healthcare. 2021; 9(6): 711. https://doi.org/10.3390/healthcare9060711
  36. Xiong T., Bai X., Wei X. et al. Exercise rehabilitation and chronic respiratory diseases: effects, mechanisms, and therapeutic benefits. Int J Chron Obstruct Pulmon Dis. 2023; 18: 1251–1266. https://doi.org/10.2147/COPD.S408325
  37. Neunhäuserer D., Patti A., Niederseer D. et al. Systemic inflammation, vascular function, and endothelial progenitor cells after an exercise training intervention in COPD. Am J Med. 2021; 134(3): e171–e180. https://doi.org/10.1016/j.amjmed.2020.07.004
  38. Moraes-Ferreira R., Brandao-Rangel M.A.R., Gibson-Alves T.G. et al. Physical Training Reduces Chronic Airway Inflammation and Mediators of Remodeling in Asthma. Oxid Med Cell Longev. 2022; 2022: 5037553. https://doi.org/10.1155/2022/5037553
  39. Cedeño de Jesús S., Almadana Pacheco V., Valido Morales A. et al. Exercise capacity and physical activity in non-cystic fibrosis bronchiectasis after a pulmonary rehabilitation home-based programme: a randomised controlled trial. Int J Environ Res Public Health. 2022; 19(17): 11039. https://doi.org/10.3390/ijerph191711039
  40. Runhaar J., Beavers D.P., Miller G.D. et al. Inflammatory cytokines mediate the effects of diet and exercise on pain and function in knee osteoarthritis independent of BMI. Osteoarthr Cartil. 2019; 27(8): 1118–1123. https://doi.org/10.1016/j.joca.2019.04.009
  41. Goh S.L., Persson M.S.M., Stocks J. et al. Efficacy and potential determinants of exercise therapy in knee and hip osteoarthritis:a systematic review and meta-analysis. Ann Phys Rehabil Med. 2019; 62(5): 356–365. https://doi.org/10.1016/j.rehab.2019.04.006
  42. Smolen J.S., Landewé R.B.M., Bijlsma J.W.J. et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis. 2020; 79(6): S685–S699. https://doi.org/10.1136/annrheumdis-2019-216655
  43. Irby A., Gutierrez J., Chamberlin C. et al. Clinical management of tendinopathy:a systematic review of systematic reviews evaluating the effectiveness of tendinopathy treatments. Scand J Med Sci Sport. 2020; 30(10): 1810–1826. https://doi.org/10.1111/sms.13734
  44. Turoń-Skrzypińska A., Mińko A., Rył A. et al. Impact of effectiveness of physical activity in a virtual environment on the regulation of sclerostin and interleukin 6 levels in haemodialysis patients. J Clin Med. 2024; 13(8): 2321. https://doi.org/10.3390/jcm13082321
  45. Meléndez-Oliva E., Sánchez-Vera Gómez-Trelles I., Segura-Orti E. et al. Effect of an aerobic and strength exercise combined program on oxidative stress and inflammatory biomarkers in patients undergoing hemodialysis:A single blind randomized controlled trial. Int. Urol. Nephrol. 2022; 54(9): 2393–2405. https://doi.org/10.1007/s11255-022-03146-z
  46. Albuquerque M.L.L., Monteiro D., Marinho D.A. et al. Effects of different protocols of physical exercise on fibromyalgia syndrome treatment: systematic review and meta-analysis of randomized controlled trials. Rheumatol Int. 2022; 42(11): 1893–1908. https://doi.org/10.1007/s00296-022-05140-1
  47. Varangot-Reille C., Suso-Martí L., Romero-Palau M. et al. Effects of different therapeutic exercise modalities on migraine or tension-type headache: a systematic review and meta-analysis with a replicability analysis. J Pain. 2022; 23(7): 1099–1122. https://doi.org/10.1016/j.jpain.2021.12.003
  48. Suso-Martí L., Núñez-Cortés R., Sánchez-Sabater A. et al. Effects of exercise-based interventions on inflammatory markers in patients with fibromyalgia: A systematic review and meta-analysis. Semin Arthritis Rheum. 2024; 65: 152377. https://doi.org/10.1016/j.semarthrit.2024.152377
  49. Kundakci B., Kaur J., Goh S.L. et al. Efficacy of nonpharmacological interventions for individual features of fibromyalgia: a systematic review and meta-analysis of randomised controlled trials. Pain. 2022; 163(8): 1432–1445. https://doi.org/10.1097/j.pain.0000000000002500
  50. Savchenko A.A., Kudryavtsev I.V., Isakov D.V. et al. Recombinant human interleukin-2 corrects NK cell phenotype and functional activity in patients with post-COVID syndrome. Pharmaceuticals (Basel). 2023; 16(4): 537. https://doi.org/10.3390/ph16040537
  51. Hong-Baik I., Úbeda-D’Ocasar E., Cimadevilla-Fernández-Pola E. et al. The effects of non-pharmacological interventions in fibromyalgia: a systematic review and metaanalysis of predominants outcomes. Biomedicines. 2023; 11(9): 2367. https://doi.org/10.3390/biomedicines11092367
  52. Chen J., Han B., Wu C. On the superiority of a combination of aerobic and resistance exercise for fibromyalgia syndrome: A network meta-analysis. Front Psychol. 2022; 13: 949256. https://doi.org/10.3389/fpsyg.2022.949256
  53. Sharova O., Smiyan O., Borén T. Immunological effects of cerebral palsy and rehabilitation exercises in children. Brain Behav Immun Health. 2021; 18: 100365. https://doi.org/10.1016/j.bbih.2021.100365
  54. Kruse A., Imery I., Corell L. et al. Circulating immune cell populations at rest and in response to acute endurance exercise in young adults with cerebral palsy. Dev Med Child Neurol. 2024; 66(7): 902–909. https://doi.org/10.1111/dmcn.15835
  55. Schlagheck M.L., Walzik D., Joisten N. et al. Cellular immune response to acute exercise: Comparison of endurance and resistance exercise. Eur J Haematol. 2020; 105(1): 75–84. https://doi.org/10.1111/ejh.13412
  56. Graff R.M., Jennings K., LaVoy E.C.P. et al. T-cell counts in response to acute cardiorespiratory or resistance exercise in physically active or physically inactive older adults: a randomized crossover study. J Appl Physiol. 2022; 133(1): 119–129. https://doi.org/10.1152/japplphysiol.00301.2021
  57. De Hoop A.M.S., Valkenet K., Dronkers J.J. et al. Effects of exercise during chemo- or radiotherapy on immune markers: a systematic review. Oncology. 2024; 102(5): 425–440. https://doi.org/10.1159/000534390
  58. Orange S.T., Jordan A.R., Odell A. et al. Acute aerobic exercise-conditioned serum reduces colon cancer cell proliferation in vitro through interleukin-6-induced regulation of DNA damage. Int J Cancer. 2022; 151(2): 265–274. https://doi.org/10.1002/ijc.33982
  59. Toffoli E.C., Sweegers M.G., Bontkes H.J. et al. Effects of physical exercise on natural killer cell activity during (neo)adjuvant chemotherapy: A randomized pilot study. Physiol Rep. 2021; 9(11): e14919. https://doi.org/10.14814/phy2.14919
  60. Zhu C., Ma H., He A. et al. Exercise in cancer prevention and anticancer therapy: Efficacy, molecular mechanisms and clinical information. Cancer Lett. 2022; 544: 215814. https://doi.org/10.1016/j.canlet.2022.215814
  61. Kim J.S., Taaffe D.R., Galvão D.A. et al. Exercise in advanced prostate cancer elevates myokine levels and suppresses in-vitro cell growth. Prostate Cancer Prostatic Dis. 2022; 25(1): 86–92. https://doi.org/10.1038/s41391-022-00504-x
  62. Schwappacher R., Dieterich W., Reljic D. et al. Muscle-derived cytokines reduce growth, viability and migratory activity of pancreatic cancer cells. Cancers (Basel). 2021; 13(15): 3820. https://doi.org/10.3390/cancers13153820
  63. Salamon G., Dougherty D., Whiting L. et al. Effects of a prescribed, supervised exercise programme on tumour disease progression in oncology patients undergoing anti-cancer therapy: a retrospective observational cohort study. Intern Med J. 2023; 53(1): 104–111. https://doi.org/10.1111/imj.15170



Creative Commons License
The content is available under the Creative Commons Attribution 4.0 License.

©


This is an open article under the CC BY 4.0 license. Published by the National Medical Research Center for Rehabilitation and Balneology.