Nutr Res Pract.  2010 Aug;4(4):259-269.

Effects of resistance training on the inflammatory response

• Calle MC
• Fernandez

Abstract

Resistance training (RT) is associated with reduced risk of low grade inflammation related diseases, such as cardiovascular disease and type 2 diabetes. The majority of the data studying cytokines and exercise comes from endurance exercise. In contrast, evidence establishing a relationship between RT and inflammation is more limited. This review focuses on the cytokine responses both following an acute bout, and after chronic RT. In addition, the effect of RT on low grade systemic inflammation such as individuals at risk for type 2 diabetes is reviewed. Cytokines are secreted proteins that influence the survival, proliferation, and differentiation of immune cells and other organ systems. Cytokines function as intracellular signals and almost all cells in the body either secrete them or have cytokine receptors. Thus, understanding cytokine role in a specific physiological situation such as a bout of RT can be exceedingly complex. The overall effect of long term RT appears to ameliorate inflammation, but the specific effects on the inflammatory cytokine, tumor necrosis factor alpha are not clear, requiring further research. Furthermore, it is critical to differentiate between chronically and acute Interleukin-6 levels and its sources. The intensity of the RT and the characteristics of the training protocol may exert singular cytokine responses and as a result different adaptations to exercise. More research is needed in the area of RT in healthy populations, specifically sorting out gender and age RT acute responses. More importantly, studies are needed in obese individuals who are at high risk of developing low grade systemic inflammatory related diseases. Assuring adherence to the RT program is essential to get the benefits after overcoming the first acute RT responses. Hence RT could be an effective way to prevent, and delay low grade systemic inflammatory related diseases.

Keyword

Cytokines; IL-6; inflammatory markers; acute resistance exercise; resistance training

MeSH Terms

Cardiovascular Diseases
Cytokines
Inflammation
Interleukin-6
Proteins
Receptors, Cytokine
Resistance Training
Tumor Necrosis Factor-alpha
Cytokines
Interleukin-6
Proteins
Receptors, Cytokine
Tumor Necrosis Factor-alpha

Reference

1. Brooks N, Layne JE, Gordon PL, Roubenoff R, Nelson ME, Castaneda-Sceppa C. Strength training improves muscle quality and insulin sensitivity in Hispanic older adults with type 2 diabetes. Int J Med Sci. 2007. 4:19–27.

2. Johnston AP, De Lisio M, Parise G. Resistance training, sarcopenia, and the mitochondrial theory of aging. Appl Physiol Nutr Metab. 2008. 33:191–199.

3. Siegrist M. Role of physical activity in the prevention of osteoporosis. Med Monatsschr Pharm. 2008. 31:259–264.

4. Mathur N, Pedersen BK. Exercise as a mean to control low-grade systemic inflammation. Mediators Inflamm. 2008. 2008:109502.

5. Sakurai T, Izawa T, Kizaki T, Ogasawara JE, Shirato K, Imaizumi K, Takahashi K, Ishida H, Ohno H. Exercise training decreases expression of inflammation-related adipokines through reduction of oxidative stress in rat white adipose tissue. Biochem Biophys Res Commun. 2009. 379:605–609.

6. Gleeson M. Immune function in sport and exercise. J Appl Physiol. 2007. 103:693–699.

7. Cooper DM, Radom-Aizik S, Schwindt C, Zaldivar F Jr. Dangerous exercise: lessons learned from dysregulated inflammatory responses to physical activity. J Appl Physiol. 2007. 103:700–709.

8. Pedersen BK, Steensberg A, Keller P, Keller C, Fischer C, Hiscock N, van Hall G, Plomgaard P, Febbraio MA. Muscle-derived interleukin-6: lipolytic, anti-inflammatory and immune regulatory effects. Pflugers Arch. 2003. 446:9–16.

9. Kenneth M, Travers P, Walport M. Janeway's Immunobiology. 2007. Seventh ed. New York: Garland Science, Taylor and Francis Group.

10. Vassilakopoulos T, Karatza MH, Katsaounou P, Kollintza A, Zakynthinos S, Roussos C. Antioxidants attenuate the plasma cytokine response to exercise in humans. J Appl Physiol. 2003. 94:1025–1032.

11. Pedersen BK, Steensberg A, Fischer C, Keller C, Keller P, Plomgaard P, Wolsk-Petersen E, Febbraio M. The metabolic role of IL-6 produced during exercise: Is IL-6 an exercise factor? Proc Nutr Soc. 2004. 63:263–267.

12. Cases N, Aguiló A, Tauler P, Sureda A, Llompart I, Pons A, Tur JA. Differential response of plasma and immune cell's vitamin E levels to physical activity and antioxidant vitamin supplementation. Eur J Clin Nutr. 2005. 59:781–788.

13. Beavers KM, Brinkley TE, Nicklas BJ. Effect of exercise training on chronic inflammation. Clin Chim Acta. 2010. 411:785–793.

14. Bloomer RJ. The role of nutritional supplements in the prevention and treatment of resistance exercise-induced skeletal muscle injury. Sports Med. 2007. 37:519–532.

15. Coffey VG, Hawley JA. The molecular bases of training adaptation. Sports Med. 2007. 37:737–763.

16. Phillips SM. Resistance exercise: good for more than just Grandma and Grandpa's muscles. Appl Physiol Nutr Metab. 2007. 32:1198–1205.

17. Alexander WS. Suppressors of cytokine signalling (SOCS) in the immune system. Nat Rev Immunol. 2002. 2:410–416.

18. Cannon JG, St. Pierre BA. Cytokines in exertion-induced skeletal muscle injury. Mol Cell Biochem. 1998. 179:159–167.

19. Pedersen BK, Febbraio MA. Muscle as an endocrine organ: Focus on muscle-derived interleukin-6. Physiol Rev. 2008. 88:1379–1406.

20. Hirose L, Nosaka K, Newton M, Laveder A, Kano M, Peake J, Suzuki K. Changes in inflammatory mediators following eccentric exercise of the elbow flexors. Exerc Immunol Rev. 2004. 10:75–90.

21. Harman E. Baechle TR, Earle RW, editors. The biomechanics of resistance exercise. Essentials of strength training and conditioning. 2000. 2nd ed. Champaign, IL: Human Kinetics.

22. Howatson G, van Someren KA. The prevention and treatment of exercise-induced muscle damage. Sports Med. 2008. 38:483–503.

23. Armstrong RB. Initial events in exercise-induced muscular injury. Med Sci Sports Exerc. 1990. 22:429–435.

24. Radom-Aizik S, Leu SY, Cooper DM, Zaldivar F Jr. Serum from exercising humans suppresses t-cell cytokine production. Cytokine. 2007. 40:75–81.

25. Petersen AM, Pedersen BK. The anti-inflammatory effect of exercise. J Appl Physiol. 2005. 98:1154–1162.

26. Miles MP. How do we solve the puzzle of unintended consequences of inflammation? Systematically. J Appl Physiol. 2008. 105:1023–1025.

27. Smith C, Kruger MJ, Smith RM, Myburgh KH. The inflammatory response to skeletal muscle injury: Illuminating complexities. Sports Med. 2008. 38:947–969.

28. Pedersen BK, Akerström TCA, Nielsen AR, Fischer CP. Role of myokines in exercise and metabolism. J Appl Physiol. 2007. 103:1093–1098.

29. Pedersen BK, Febbraio M. Muscle-derived interleukin-6--a possible link between skeletal muscle, adipose tissue, liver, and brain. Brain Behav Immun. 2005. 19:371–376.

30. Brandt C, Pedersen BK. The role of exercise-induced myokines in muscle homeostasis and the defense against chronic diseases. J Biomed Biotechnol. 2010. 2010:520258.

31. Arend WP. The balance between IL-1 and IL-1Ra in disease. Cytokine Growth Fact Rev. 2002. 13:323–340.

32. Stewart LK, Flynn MG, Campbell WW, Craig BA, Robinson JP, Timmerman KL, McFarlin BK, Coen PM, Talbert E. The influence of exercise training on inflammatory cytokines and C-reactive protein. Med Sci Sports Exerc. 2007. 39:1714–1719.

33. Izquierdo M, Ibañez J, Calbet JAL, Navarro-Amezqueta I, González-Izal M, Idoate F, Häkkinen K, Kraemer WJ, Palacios-Sarrasqueta M, Almar M, Gorostiaga EM. Cytokine and hormone responses to resistance training. Eur J Appl Physiol. 2009. 107:397–409.

34. Pedersen BK, Fischer CP. Beneficial health effects of exercise - the role of IL-6 as a myokine. Trends Pharmacol Sci. 2007. 28:152–156.

35. Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006. 444:860–867.

36. Steinacker JM, Lormes W, Reissnecker S, Liu Y. New aspects of the hormone and cytokine response to training. Eur J Appl Physiol. 2004. 91:382–391.

37. Perrier S, Darakhshan F, Hajduch E. IL-1 receptor antagonist in metabolic diseases: Dr Jekyll or Mr Hyde? FEBS Lett. 2006. 580:6289–6294.

38. Nielsen AR, Pedersen BK. The biological roles of exercise-induced cytokines: IL-6, IL-8, and IL-15. Appl Physiol Nutr Metab. 2007. 32:833–839.

39. Riechman SE, Balasekaran G, Roth SM, Ferrell RE. Association of interleukin-15 protein and interleukin-15 receptor genetic variation with resistance exercise training responses. J Appl Physiol. 2004. 97:2214–2219.

40. Bastard JP, Maachi M, Lagathu C, Kim MJ, Caron M, Vidal H, Capeau J, Feve B. Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw. 2006. 17:4–12.

41. Rieusset J, Bouzakri K, Chevillotte E, Ricard N, Jacquet D, Bastard JP, Laville M, Vidal H. Suppressor of cytokine signaling 3 expression and insulin resistance in skeletal muscle of obese and type 2 diabetic patients. Diabetes. 2004. 53:2232–2241.

42. Fox CS, Coady S, Sorlie PD, Levy D, Meigs JB, D'Agostino RB Sr, Wilson PWF, Savage PJ. Trends in cardiovascular complications of diabetes. JAMA. 2004. 292:2495–2499.

43. Ploeger HE, Takken T, de Greef MH, Timmons BW. The effects of acute and chronic exercise on inflammatory markers in children and adults with a chronic inflammatory disease: a systematic review. Exerc Immunol Rev. 2009. 15:6–41.

44. Koopman R, Manders RJ, Zorenc AH, Hul GB, Kuipers H, Keizer HA, van Loon LJ. A single session of resistance exercise enhances insulin sensitivity for at least 24 h in healthy men. Eur J Appl Physiol. 2005. 94:180–187.

45. Sigal RJ, Kenny GP, Boulé NG, Wells GA, Prud'homme D, Fortier M, Reid RD, Tulloch H, Coyle D, Phillips P, Jennings A, Jaffey J. Effects of aerobic training, resistance training, or both on glycemic control in type 2 diabetes: a randomized trial. Ann Intern Med. 2007. 147:357–369.

46. Kones R. The Jupiter study, CRP screening, and aggressive statin therapy-implications for the primary prevention of cardiovascular disease. Ther Adv Cardiovasc Dis. 2009. 3:309–315.

47. Peake JM, Nosaka K, Muthalib M, Suzuki K. Systemic inflammatory responses to maximal versus submaximal lengthening contractions of the elbow flexors. Exerc Immunol Rev. 2006. 12:72–85.

48. de Salles BF, Simão R, Fleck SJ, Dias I, Kraemer-Aguiar LG, Bouskela E. Effects of resistance training on cytokines. Int J Sports Med. 2010. 31:441–450.

49. Kraemer WJ, Ratamess NA. Fundamentals of resistance training: progression and exercise prescription. Med Sci Sports Exerc. 2004. 36:674–688.

50. Levinger I, Goodman C, Peake J, Garnham A, Hare DL, Jerums G, Selig S. Inflammation, hepatic enzymes and resistance training in individuals with metabolic risk factors. Diabet Med. 2009. 26:220–227.

51. Olson TP, Dengel DR, Leon AS, Schmitz KH. Changes in inflammatory biomarkers following one-year of moderate resistance training in overweight women. Int J Obes. 2007. 31:996–1003.

52. Timmons BW, Tarnopolsky MA, Snider DP, Bar-Or O. Immunological changes in response to exercise: Influence of age, puberty, and gender. Med Sci Sports Exerc. 2006. 38:293–304.

53. Colbert LH, Visser M, Simonsick EM, Tracy RP, Newman AB, Kritchevsky SB, Pahor M, Taaffe DR, Brach J, Rubin S, Harris TB. Physical activity, exercise, and inflammatory markers in older adults: Findings from the health, aging and body composition study. J Am Geriatr Soc. 2004. 52:1098–1104.

54. Woods JA, Lu Q, Lowder T. Exercise-induced modulation of macrophage function. Immunol Cell Biol. 2000. 78:545–553.

55. Palmer DC, Restifo NP. Suppressors of cytokine signaling (SOCS) in T cell differentiation, maturation, and function. Trends Immunol. 2009. 30:592–602.

56. Rønn SG, Billestrup N, Mandrup-Poulsen T. Diabetes and suppressors of cytokine signaling proteins. Diabetes. 2007. 56:541–548.

57. Pedersen BK. IL-6 signalling in exercise and disease. Biochem Soc Trans. 2007. 35:1295–1297.

58. Kelly M, Keller C, Avilucea PR, Keller P, Luo Z, Xiang X, Giralt M, Hidalgo J, Saha AK, Pedersen BK, Ruderman NB. AMPK activity is diminished in tissues of IL-6 knockout mice: the effect of exercise. Biochem Biophys Res Commun. 2004. 320:449–454.

59. Krook A, Long YC, Zierath JR. Skeletal muscle AMP kinase as a target to prevent pathogenesis of Type 2 diabetes. Expert Rev Endocrinol Metab. 2007. 2:477–485.

60. Serrano AL, Baeza-Raja B, Perdiguero E, Jardí M, Muñoz-Cánoves P. Interleukin-6 Is an Essential Regulator of Satellite Cell-Mediated Skeletal Muscle Hypertrophy. Cell Metab. 2008. 7:33–44.

61. Lehmann MJ, Lormes W, Opitz-Gress A, Steinacker JM, Netzer N, Foster C, Gastmann U. Training and overtraining: an overview and experimental results in endurance sports. J Sports Med Phys Fitness. 1997. 37:7–17.

62. Ramel A, Wagner KH, Elmadfa I. Correlations between plasma noradrenaline concentrations, antioxidants, and neutrophil counts after submaximal resistance exercise in men. Br J Sports Med. 2004. 38:E22.

63. Gomez-Cabrera MC, Domenech E, Viña J. Moderate exercise is an antioxidant: Upregulation of antioxidant genes by training. Free Radic Biol Med. 2008. 44:126–131.

64. Phillips MD, Mitchell JB, Currie-Elolf LM, Yellott RC, Hubing KA. Influence of commonly employed resistance exercise protocols on circulating IL-6 and indices of insulin sensitivity. J Strength Cond Res. 2010. 24:1091–1101.

65. Uchida MC, Nosaka K, Ugrinowitsch C, Yamashita A, Martins E Jr, Moriscot AS, Aoki MS. Effect of bench press exercise intensity on muscle soreness and inflammatory mediators. J Sports Sci. 2009. 27:499–507.

66. MacIntyre DL, Sorichter S, Mair J, Berg A, McKenzie DC. Markers of inflammation and myofibrillar proteins following eccentric exercise in humans. Eur J Appl Physiol. 2001. 84:180–186.

67. Buford TW, Cooke MB, Willoughby DS. Resistance exercise-induced changes of inflammatory gene expression within human skeletal muscle. Eur J Appl Physiol. 2009. 107:463–471.

68. Nielsen AR, Mounier R, Plomgaard P, Mortensen OH, Penkowa M, Speerschneider T, Pilegaard H, Pedersen BK. Expression of interleukin-15 in human skeletal muscle - effect of exercise and muscle fibre type composition. J Physiol. 2007. 584:305–312.

69. Smith LL, Anwar A, Fragen M, Rananto C, Johnson R, Holbert D. Cytokines and cell adhesion molecules associated with high-intensity eccentric exercise. Eur J Appl Physiol. 2000. 82:61–67.

70. Robert Harris GD. Baechle TR, Earle RW, editors. Neuromuscular anatomy and adaptations to conditioning. Essentials of strength training and conditioning. 2000. Champaign, IL: Human Kinetics.

71. Prokopchuk O, Liu Y, Wang L, Wirth K, Schmidtbleicher D, Steinacker JM. Skeletal muscle IL-4, IL-4Ralpha, IL-13 and IL-13Ralpha1 expression and response to strength training. Exerc Immunol Rev. 2007. 13:67–75.

72. Peake JM, Suzuki K, Hordern M, Wilson G, Nosaka K, Coombes JS. Plasma cytokine changes in relation to exercise intensity and muscle damage. Eur J Appl Physiol. 2005. 95:514–521.

73. Gokhale R, Chandrashekara S, Vasanthakumar KC. Cytokine response to strenuous exercise in athletes and non-athletes-an adaptive response. Cytokine. 2007. 40:123–127.

74. Nieman DC, Davis JM, Brown VA, Henson DA, Dumke CL, Utter AC, Vinci DM, Downs MF, Smith JC, Carson J, Brown A, McAnulty SR, McAnulty LS. Influence of carbohydrate ingestion on immune changes after 2 h of intensive resistance training. J Appl Physiol. 2004. 96:1292–1298.

75. Horsley V, Jansen KM, Mills ST, Pavlath GK. IL-4 acts as a myoblast recruitment factor during mammalian muscle growth. Cell. 2003. 113:483–494.

76. Wynn TA. IL-13 effector functions. Annu Rev Immunol. 2003. 21:425–456.

77. Kirwan JP, Del Aguila LF. Insulin signalling, exercise and cellular integrity. Biochem Soc Trans. 2003. 31:1281–1285.

78. Calle MC, Fernandez ML, Kraemer WJ, Volk BM, Kupchak B, Volek JS. Resistance training improves the inflammatory response to an acute resistance exercise bout in healthy young adults. FASEB J. 2010. 24:743.2.

79. Izeboud CA, Monshouwer M, Van Miert AS, Witkamp RF. The β-adrenoceptor agonist clenbuterol is a potent inhibitor of the LPS-induced production of TNF-α and IL-6 in vitro and in vivo. Inflamm Res. 1999. 48:497–502.

80. Boyle JP, Honeycutt AA, Narayan KM, Hoerger TJ, Geiss LS, Chen H, Thompson TJ. Projection of diabetes burden through 2050: impact of changing demography and disease prevalence in the U.S. Diabetes Care. 2001. 24:1936–1940.