The Effect of Exercise Training on the Levels of Anti-Inflammatory Factors (IL-4 and IL-10): A Meta-Analysis Study

Document Type : Review Article

Authors

1 Department of Exercise Physiology, University of Kurdistan, Sanandaj 66177-15175, Iran. ORCID No: https://orcid.org/0000-0002-4302-1472

2 Department of Physical Education and Sport Sciences, Islamic Azad University, Marivan Branch, Marivan, Iran.

3 Department of Exercise Physiology, University of Kurdistan, Sanandaj, Iran.

Abstract

Background: Anti-inflammatory markers play a crucial role in chronic diseases.. Regular training is a valuable method to control inflammation.
Aim: This meta-analysis aims to explore the impact of exercise training on anti-inflammatory indicators like IL-10 and IL-4.
Martials and methods: Various databases, including PubMed, Cochrane, Embase, Web of Science, EBSCO, and Google Scholar, were systematically searched for randomized controlled trials from 2007 to 2023. Studies focusing on IL-10 and IL-4 indicators in individuals undergoing exercise training were selected. According to the study inclusion criteria, ultimately, 40 articles were finally selected as study samples for the meta-analysis. The meta-analysis was conducted using fixed and random effects models to analyze the effect sizes, taking into account factors such as age, gender, health status, type and duration of exercise, and BM..
Results: Aerobic training significantly increased IL-10 levels (p=0.00, 95% CI=0.267:0.723, ES=0.495), while the increase after resistance training was not significant (ES=0.295, 95% CI-0.020:0.610, p=0.067). Both aerobic training (ES=-282, 95% CI=-0.795:0.185, p=0.237) and resistance training (ES=0.227, 95% CI=-0.389:0.843, p=0.471) had no significant effect onIL-4 levels. Subgroup analysis revealed a significant increase in IL-10 associated withBMI subgroups (p=0.019), with the highest increase in BMI group 18 to 25 (p=0.001). Subgroup meta-analysis for IL-4 showed no significant differences between subgroups (p>0.05).
Conclusion: Aerobic training was associated with a significant increase in IL-10 levels in healthy and unhealthy subjects, but aerobic and resistance training had no significant effect on IL-4 levels. Further randomized controlled studies are essential, especially focusing on resistance training and different training scenarios.

Keywords

References

  1. Ellulu MS, Patimah I, Khaza’ai H, Rahmat A, Abed Y. Obesity and inflammation: the linking mechanism and the complications. Archives of medical science. 2017;13(4):851-63.
  2. Pournemati P, Hooshmand Moghadam B. The Effect of 12 Weeks of Interval and Continuous Training on Serum Levels of Interleukin-17 and Interleukin-10 in Postmenopausal Breast Cancer Survivors: A Clinical Trial. Iranian Journal of Breast Diseases. 2021;14(2):4-15.
  3. Ioannidou A, Goulielmaki E, Garinis GA. DNA damage: from chronic inflammation to age-related deterioration. Frontiers in genetics. 2016;7:187.
  4. Medzhitov R. Origin and physiological roles of inflammation. Nature. 2008;454(7203):428-35.
  5. Candido J, Hagemann T. Cancer-related inflammation. Journal of clinical immunology. 2013;33:79-84.
  6. Chen L, Liu H, Yuan M, Lu W, Wang J, Wang T. The roles of interleukins in perfusion recovery after peripheral arterial disease. Bioscience Reports. 2018;38(1):BSR20171455.
  7. Allen J, Sun Y, Woods JA. Exercise and the regulation of inflammatory responses. Progress in molecular biology and translational science. 2015;135:337-54.
  8. Gandhi NA, Bennett BL, Graham NM, Pirozzi G, Stahl N, Yancopoulos GD. Targeting key proximal drivers of type 2 inflammation in disease. Nature reviews Drug discovery. 2016;15(1):35-50.
  9. Sabat R, Grütz G, Warszawska K, Kirsch S, Witte E, Wolk K, et al. Biology of interleukin-10. Cytokine & growth factor reviews. 2010;21(5):331-44.
  10. Belghith M, Bahrini K, Kchaou M, Maghrebi O, Belal S, Barbouche MR. Cerebrospinal fluid IL-10 as an early stage discriminative marker between multiple sclerosis and neuro-Behçet disease. Cytokine. 2018;108:160-7.
  11. Mocellin S, Marincola FM, Young HA. Interleukin-10 and the immune response against cancer: a counterpoint. Journal of leukocyte biology. 2005;78(5):1043-51.
  12. Shafieerad E, Isanejad A, Nasiri E. The effects of 8 weeks of endurance exercise training on IL-10 level and body composition of sedentary overweight women. Journal of Practical Studies of Biosciences in Sport. 2018;6(11):49-57.
  13. Branch T. Synergistic Effect of Endurance Training Combined with Curcumin on Intratumoral Expression of Interleukin-4 (Il4) and Stat-6 in Female Mice with Breast Cancer. 2020.
  14. Bao L, Shi VY, Chan LS. IL-4 up-regulates epidermal chemotactic, angiogenic, and pro-inflammatory genes and down-regulates antimicrobial genes in vivo and in vitro: relevant in the pathogenesis of atopic dermatitis. Cytokine. 2013;61(2):419-25.
  15. Zhang J-H, Zhang M, Wang Y-N, Zhang X-Y. Correlation between IL-4 and IL-13 gene polymorphisms and asthma in Uygur children in Xinjiang. Experimental and therapeutic medicine. 2019;17(2):1374-82.
  16. Traub B, Sun L, Ma Y, Xu P, Lemke J, Paschke S, et al. Endogenously expressed IL-4Rα promotes the malignant phenotype of human pancreatic cancer in vitro and in vivo. International journal of molecular sciences. 2017;18(4):716.
  17. Gandhi NA, Pirozzi G, Graham NM. Commonality of the IL-4/IL-13 pathway in atopic diseases. Expert review of clinical immunology. 2017;13(5):425-37.
  18. Zheng G, Qiu P, Xia R, Lin H, Ye B, Tao J, et al. Effect of aerobic exercise on inflammatory markers in healthy middle-aged and older adults: a systematic review and meta-analysis of randomized controlled trials. Frontiers in aging neuroscience. 2019;11:98.
  19. Streese L, Deiseroth A, Schäfer J, Schmidt-Trucksäss A, Hanssen H. Exercise, arterial crosstalk-modulation, and inflammation in an aging population: the ExAMIN AGE study. Frontiers in physiology. 2018;9:116.
  20. Bayat H, Khalounejad H, Babaei M, Arnavazi yamchi N, Azarbayjani MA. Interactive effect of a period of high-intensity interval training and cinnamon supplementation on the levels of some inflammatory and anti-inflammatory markers in overweight men. Research in Exercise Nutrition. 2022;1(2):35-42.
  21. Alizadeh H, Safarzade A. High intensity intermittent training induces anti-inflammatory cytokine responses and improves body composition in overweight adolescent boys. Hormone Molecular Biology and Clinical Investigation. 2019;39(3):20190004.
  22. Kadoglou NP, Iliadis F, Angelopoulou N, Perrea D, Ampatzidis G, Liapis CD, et al. The anti-inflammatory effects of exercise training in patients with type 2 diabetes mellitus. European Journal of Preventive Cardiology. 2007;14(6):837-43.
  23. Rahimi MR, Beaven CM. Caffeine Modifies the Immune and Anti-inflammatory Responses to Short Incremental Cycling Exercise Until Exhaustion in Humans: A Pilot Study. Journal of Science in Sport and Exercise. 2023:1-5.
  24. Babaei S, Fattahpou marandi M. The effect of 12 weeks of aerobic training and zinc supplementation on interleukin 1 beta and TNF alpha in women with type 2 diabetes. Research in Exercise Nutrition. 2022;1(3):33-41.
  25. Rahimi MR, Shoker-Nejad H. Effects of β-Hydroxy-β-Methylbutyrate Supplementation on IL-4, IL-10 and TGF-β1 during Resistance Exercise in Athletes. Research in Exercise Nutrition. 2022;1(1):40-21.
  26. Conroy SM, Courneya KS, Brenner DR, Shaw E, O'Reilly R, Yasui Y, et al. Impact of aerobic exercise on levels of IL‐4 and IL‐10: results from two randomized intervention trials. Cancer medicine. 2016;5(9):2385-97.
  27. Alvandi H, Salehzadeh K, Najafzade M, Kalani AT. The effect of strength training on anti-inflammatory cytokines, cortisol and testosterone in overweight men. European Journal of Experimental Biology. 2014;4(1):296-302.
  28. Monteiro-Junior RS, de Tarso Maciel-Pinheiro P, Portugal EdMM, da Silva Figueiredo LF, Terra R, Carneiro LS, et al. Effect of exercise on inflammatory profile of older persons: systematic review and meta-analyses. Journal of Physical Activity and Health. 2018;15(1):64-71.
  29. Walker AE. Modulation of vascular endothelial function by chronic low-grade inflammation in healthy middle-aged and older adults: influence of habitual aerobic exercise: University of Colorado at Boulder; 2010.
  30. Maher CG, Sherrington C, Herbert RD, Moseley AM, Elkins M. Reliability of the PEDro scale for rating quality of randomized controlled trials. Physical therapy. 2003;83(8):713-21.
  31. Verma R, Balakrishnan L, Sharma K, Khan AA, Advani J, Gowda H, et al. A network map of Interleukin-10 signaling pathway. Journal of cell communication and signaling. 2016;10:61-7.
  32. Laird BJ, Scott AC, Colvin LA, McKeon A-L, Murray GD, Fearon KC, et al. Cancer pain and its relationship to systemic inflammation: an exploratory study. PAIN®. 2011;152(2):460-3.
  33. Brandt C, Pedersen BK. The role of exercise‐induced myokines in muscle homeostasis and the defense against chronic diseases. BioMed Research International. 2010;2010(1):520258.
  34. Petersen AMW, Pedersen BK. The anti-inflammatory effect of exercise. Journal of applied physiology. 2005;98(4):1154-62.
  35. Murray PJ. The primary mechanism of the IL-10-regulated antiinflammatory response is to selectively inhibit transcription. Proceedings of the National Academy of Sciences. 2005;102(24):8686-91.
  36. Alizaei Yousefabadi H, Niyazi A, Alaee S, Fathi M, Mohammad Rahimi GR. Anti-inflammatory effects of exercise on metabolic syndrome patients: a systematic review and meta-analysis. Biological research for nursing. 2021;23(2):280-92.
  37. Khalafi M, Sakhaei MH, Symonds ME, Noori Mofrad SR, Liu Y, Korivi M. Impact of exercise in hypoxia on inflammatory cytokines in adults: a systematic review and meta-analysis. Sports Medicine-Open. 2023;9(1):50.
  38. Nakajima T, Kurano M, Hasegawa T, Takano H, Iida H, Yasuda T, et al. Pentraxin3 and high-sensitive C-reactive protein are independent inflammatory markers released during high-intensity exercise. European journal of applied physiology. 2010;110:905-13.
  39. Handzlik MK, Shaw AJ, Dungey M, Bishop NC, Gleeson M. The influence of exercise training status on antigen-stimulated IL-10 production in whole blood culture and numbers of circulating regulatory T cells. European journal of applied physiology. 2013;113:1839-48.
  40. Hirose L, Nosaka K, Newton M, Laveder A, Kano M, Peake J, et al. Changes in inflammatory mediators following eccentric exercise of the elbow flexors. Exerc Immunol Rev. 2004;10(75-90):20.
  41. Trayhurn P, Wood I. Signalling role of adipose tissue: adipokines and inflammation in obesity. Biochemical Society Transactions. 2005;33(5):1078-81.
  42. Tabares-Guevara JH, Jaramillo JC, Ospina-Quintero L, Piedrahíta-Ochoa CA, García-Valencia N, Bautista-Erazo DE, et al. IL-10-Dependent amelioration of chronic inflammatory disease by microdose subcutaneous delivery of a prototypic immunoregulatory small molecule. Frontiers in Immunology. 2021;12:708955.
  43. Carlini V, Noonan DM, Abdalalem E, Goletti D, Sansone C, Calabrone L, et al. The multifaceted nature of IL-10: regulation, role in immunological homeostasis and its relevance to cancer, COVID-19 and post-COVID conditions. Frontiers in immunology. 2023;14:1161067.
  44. Sun H, Wu Y, Zhang Y, Ni B. IL-10-Producing ILCs: Molecular mechanisms and disease relevance. Frontiers in Immunology. 2021;12:650200.
  45. Wang S, Zhou H, He H. Effect of exercise training on body composition and inflammatory cytokine levels in overweight and obese individuals: a systematic review and network meta-analysis. Frontiers in immunology. 2022;13:921085.
  46. Ringleb M, Javelle F, Haunhorst S, Bloch W, Fennen L, Baumgart S, et al. Acute resistance exercise-induced changes in IL-6, IL-10, and IL-1ra in healthy adults: a systematic review and meta-analysis. medRxiv. 2023:2023.05. 10.23289790.
  47. Forti LN, Van Roie E, Njemini R, Coudyzer W, Beyer I, Delecluse C, et al. Effects of resistance training at different loads on inflammatory markers in young adults. European journal of applied physiology. 2017;117:511-9.
  48. Hasanli S, Hojjati S, Koushkie Jahromi M. The effect of exercise and psychological stress on anti-and proinflammatory cytokines. Neuroimmunomodulation. 2021;27(4):186-93.
  49. Biedermann T, Röcken M. Pro-and anti-inflammatory effects of IL-4: from studies in mice to therapy of autoimmune diseases in humans. Animal Models of T Cell-Mediated Skin Diseases. 2005:235-42.
  50. Iwaszko M, Biały S, Bogunia-Kubik K. Significance of interleukin (IL)-4 and IL-13 in inflammatory arthritis. Cells. 2021;10(11):3000.
  51. Dawidowski B, Górniak A, Podwalski P, Lebiecka Z, Misiak B, Samochowiec J. The role of cytokines in the pathogenesis of schizophrenia. Journal of Clinical Medicine. 2021;10(17):3849.
  52. Cullen T, Thomas AW, Webb R, Hughes MG. Interleukin-6 and associated cytokine responses to an acute bout of high-intensity interval exercise: the effect of exercise intensity and volume. Applied physiology, nutrition, and metabolism. 2016;41(8):803-8.
  53. Docherty S, Harley R, McAuley JJ, Crowe LA, Pedret C, Kirwan PD, et al. The effect of exercise on cytokines: implications for musculoskeletal health: a narrative review. BMC Sports Science, Medicine and Rehabilitation. 2022;14(1):5.
Sport Sciences and Health Research
Volume 17, Issue 2
July 2025
Pages 30-49

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