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The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease

Key Points

  • Physical inactivity increases the risk of type 2 diabetes, cardiovascular diseases, chronic obstructive pulmonary disease, colon cancer, breast cancer, dementia and depression.

  • Physical inactivity leads to the accumulation of visceral fat and consequently the activation of a network of inflammatory pathways. Chronic inflammation promotes the development of insulin resistance, atherosclerosis, neurodegeneration and tumour growth, and subsequently the development of a number of diseases associated with physical inactivity.

  • The protective effect of exercise against chronic inflammation-associated diseases may, to some extent, be ascribed to an anti-inflammatory effect of regular exercise. The anti-inflammatory effect of regular exercise may be mediated by a reduction in visceral fat mass (with a subsequent decreased release of adipokines from adipose tissue) and/or by the induction of an anti-inflammatory environment with each bout of exercise.

  • Possible mechanisms by which exercise exerts its anti-inflammatory effect include: release of interleukin-6 (IL-6) into the circulation from contracting muscle fibres and subsequent increases in circulating levels of IL-10 and IL-1 receptor antagonist; increased circulating numbers of IL-10-secreting regulatory T cells; downregulation of Toll-like receptor expression on monocytes and inhibition of downstream responses (such as pro-inflammatory cytokine production, antigen presentation and co-stimulatory molecule expression); reduction in the circulating numbers of pro-inflammatory monocytes; and inhibition of monocyte and/or macrophage infiltration into adipose tissue.

  • Although regular moderate exercise is associated with a reduced incidence of infection compared with a completely sedentary state, the long hours of hard training undertaken by elite athletes appear to make these individuals more susceptible to infections. This is also probably attributable to the anti-inflammatory effects of exercise inducing a degree of immunosuppression.

  • Important remaining questions on the anti-inflammatory effects of exercise include: what is the independent contribution of an exercise-induced reduction in visceral fat versus other exercise-induced anti-inflammatory mechanisms? What is the relative importance of the different anti-inflammatory mechanisms? What modes, intensities and durations of exercise are required to optimize the anti-inflammatory effects of exercise?

Abstract

Regular exercise reduces the risk of chronic metabolic and cardiorespiratory diseases, in part because exercise exerts anti-inflammatory effects. However, these effects are also likely to be responsible for the suppressed immunity that makes elite athletes more susceptible to infections. The anti-inflammatory effects of regular exercise may be mediated via both a reduction in visceral fat mass (with a subsequent decreased release of adipokines) and the induction of an anti-inflammatory environment with each bout of exercise. In this Review, we focus on the known mechanisms by which exercise — both acute and chronic — exerts its anti-inflammatory effects, and we discuss the implications of these effects for the prevention and treatment of disease.

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Figure 1: The effect of diet and physical activity on inflammation and disease.
Figure 2: Potential mechanisms contributing to the anti-inflammatory effects of exercise.

References

  1. Mathis, D. & Shoelson, S. Immunometabolism: an emerging frontier. Nature Rev. Immunol. 11, 81–93 (2011).

    Article  CAS  Google Scholar 

  2. Hotamisligil, G. S. Inflammation and metabolic disorders. Nature 444, 860–867 (2006).

    Article  CAS  PubMed  Google Scholar 

  3. Shoelson, S. E., Lee, J. & Goldfine, A. B. Inflammation and insulin resistance. J. Clin. Invest. 116, 1793–1801 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Ouchi, N., Parker, J. L., Lugus, J. J. & Walsk, K. Adipokines in inflammation and metabolic disease. Nature Rev. Immunol. 11, 85–97 (2011).

    Article  CAS  Google Scholar 

  5. Rook, G. A. & Dalgleish, A. Infection, immunoregulation, and cancer. Immunol. Rev. 240, 141–159 (2011).

    Article  CAS  PubMed  Google Scholar 

  6. Leonard, B. E. Inflammation, depression and dementia: are they connected? Neurochem. Res. 32, 1749–1756 (2007).

    Article  CAS  PubMed  Google Scholar 

  7. Pradhan, A. D., Manson, J. E., Rifai, N., Buring, J. E. & Ridker, P. M. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 286, 327–334 (2001).

    Article  CAS  PubMed  Google Scholar 

  8. Pedersen, B. K. & Saltin, B. Evidence for prescribing exercise as therapy in chronic disease. Scand. J. Med. Sci. Sports 16 (Suppl. 1), 5–65 (2006).

    Google Scholar 

  9. Hardman, A. E. & Stensel, D. J. Physical Activity and Health: The Evidence Explained 2nd edn 120–121 (Routledge, Abingdon, Oxon, 2009).

    Book  Google Scholar 

  10. Warren, T. Y. et al. Sedentary behaviors increase risk of cardiovascular disease mortality in men. Med. Sci. Sports Exerc. 42, 879–885 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Walsh, N. P. et al. Position statement. Part one: immune function and exercise. Exerc. Immunol. Rev. 17, 1–65 (2011). This review provides the most up-to-date scientific consensus on the effects of exercise on immune function.

    Google Scholar 

  12. Jonas, S. & Phillips, E. M. ACSM's Exercise is Medicine: A Clinician's Guide to Exercise Prescription. (Lippincott Williams & Wilkins, Hagerstown, Maryland, 2009).

    Google Scholar 

  13. Kraus, W. E. et al. Effects of the amount and intensity of exercise on plasma lipoproteins. N. Engl. J. Med. 347, 1483–1492 (2002).

    Article  CAS  PubMed  Google Scholar 

  14. Kasapis, C. & Thompson, P. D. The effects of physical activity on serum C-reactive protein and inflammatory markers: a systematic review. J. Am. Coll. Cardiol. 45, 1563–1569 (2005).

    Article  CAS  PubMed  Google Scholar 

  15. Petersen, A. M. & Pedersen, B. K. The anti-inflammatory effect of exercise. J. Appl. Physiol. 98, 1154–1162 (2005).

    Article  CAS  PubMed  Google Scholar 

  16. Mathur, M. & Pedersen, B. K. Exercise as a mean to control low-grade inflammation. Mediators Inflamm. 2008, 109502 (2008).

    Article  PubMed  CAS  Google Scholar 

  17. Flynn, M. G. & McFarlin, B. K. Toll-like receptor 4: link to the anti-inflammatory effects of exercise? Exerc. Sport Sci. Rev. 34, 176–181 (2006).

    Article  PubMed  Google Scholar 

  18. Pedersen, B. K. & Febbraio, M. A. Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiol. Rev. 88, 1379–1406 (2008).

    Article  CAS  PubMed  Google Scholar 

  19. Gleeson, M., McFarlin, B. K. & Flynn, M. G. Exercise and Toll-like receptors. Exerc. Immunol. Rev. 12, 34–53 (2006).

    PubMed  Google Scholar 

  20. Kawanishi, N., Yano, H., Yokogawa, Y. & Suzuki, K. Exercise training inhibits inflammation in adipose tissue via both suppression of macrophage infiltration and acceleration of phenotypic switching from M1 to M2 macrophages in high-fat-diet-induced obese mice. Exerc. Immunol. Rev. 16, 105–118 (2010). This study demonstrates that exercise reduces inflammation in adipose tissue via two separate mechanisms.

    PubMed  Google Scholar 

  21. Timmerman, K. L., Flynn, M. G., Coen, P. M., Markofski, M. M. & Pence, B. D. Exercise training-induced lowering of inflammatory (CD14+CD16+) monocytes: a role in the anti-inflammatory influence of exercise? Leukoc. Biol. 84, 1271–1278 (2008).

    Article  CAS  Google Scholar 

  22. Yeh, S.-H., Chuang, H., Lin, L.-W., Hsiao, C.-Y. & Eng, H. L. Regular tai chi chuan exercise enhances functional mobility and CD4CD25 regulatory T cells. Br. J. Sports Med. 40, 239–243 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  23. Wang, J. et al. Effect of exercise training intensity on murine T-regulatory cells and vaccination response. Scand. J. Med. Sci. Sports 16 Mar 2011 (doi:10.1111/j.1600-0838.2010.01288.x). This study indicates that intensive exercise training increases circulating numbers of regulatory T cells.

    Article  Google Scholar 

  24. Pischon, H. et al. General and abdominal adiposity and risk of death in Europe. N. Engl. J. Med. 359, 2105–2120 (2008).

    Article  CAS  PubMed  Google Scholar 

  25. Bays, H. E. “Sick fat”, metabolic disease, and atherosclerosis. Am. J. Med. 122, S26–S37 (2009).

    Article  CAS  PubMed  Google Scholar 

  26. Haffner, S. M. Abdominal adiposity and cardiometabolic risk: do we have all the answers? Am. J. Med. 120, S10–S16 (2007).

    Article  CAS  PubMed  Google Scholar 

  27. Whitmer, R. A. et al. Central obesity and increased risk of dementia more than three decades later. Neurology 71, 1057–1064 (2008).

    Article  CAS  PubMed  Google Scholar 

  28. Xue, F. & Michels, K. B. Diabetes, metabolic syndrome, and breast cancer: a review of the current evidence. Am. J. Clin. Nutr. 86, S823–S835 (2007).

    Article  PubMed  Google Scholar 

  29. Yudkin, J. S. Inflammation, obesity, and the metabolic syndrome. Horm. Metab. Res. 39, 707–709 (2007).

    Article  CAS  PubMed  Google Scholar 

  30. Ross, R. & Bradshaw, A. J. The future of obesity reduction: beyond weight loss. Nature Rev. Endocrinol. 5, 319–325 (2009).

    Article  Google Scholar 

  31. Mujumdar, P. P., Duerksen, P. J., Firek, A. F. & Hessingere, D. A. Long-term, progressive, aerobic training increases adiponectin in middle-aged, overweight, untrained males and females. Scand. J. Clin. Lab. Invest. 71, 101–107 (2011).

    Article  CAS  PubMed  Google Scholar 

  32. Ben Ounis, O. et al. Two-month effects of individualized exercise training with or without caloric restriction on plasma adipocytokine levels in obese female adolescents. Ann. Endocrinol. 70, 235–241 (2009).

    Article  CAS  Google Scholar 

  33. Lim, S. et al. Insulin-sensitizing effects of exercise on adiponectin and retinol-binding protein-4 concentrations in young and middle-aged women. J. Clin. Endocrinol. Metab. 93, 2263–2268 (2008).

    Article  CAS  PubMed  Google Scholar 

  34. Mohamed-Ali, V. et al. Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-α, in vivo. J. Clin. Endocrinol. Metab. 82, 4196–4200 (1997).

    CAS  PubMed  Google Scholar 

  35. Fried, S. K., Bunkin, D. A. & Greenberg, A. S. Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid. J. Clin. Endocrinol. Metab. 83, 847–850 (1998).

    CAS  PubMed  Google Scholar 

  36. Pedersen, B. K. Edward F. Adolph Distinguished Lecture: Muscle as an endocrine organ: IL-6 and other myokines. J. Appl. Physiol. 107, 1006–1014 (2009).

    Article  CAS  PubMed  Google Scholar 

  37. Fischer, C. P. Interleukin-6 in acute exercise and training: what is the biological relevance? Exerc. Immunol. Rev. 12, 6–33 (2006).

    PubMed  Google Scholar 

  38. Meckel, Y. et al. The effect of a brief sprint interval exercise on growth factors and inflammatory mediators. J. Strength Cond. Res. 23, 225–230 (2009).

    Article  PubMed  Google Scholar 

  39. Keller, C. et al. Effect of exercise, training, and glycogen availability on IL-6 receptor expression in human skeletal muscle. J. Appl. Physiol. 99, 2075–2079 (2005).

    Article  CAS  PubMed  Google Scholar 

  40. Pedersen, B. K. & Fischer, C. P. Beneficial health effects of exercise — the role of IL-6 as a myokine. Trends Pharmacol. Sci. 28, 152–156 (2007). This is an important review that introduces the concept of skeletal muscle acting as an endocrine organ.

    Article  CAS  PubMed  Google Scholar 

  41. Steensberg, A., Fischer, C. P., Keller, C., Moller, K. & Pedersen, B. K. IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans. Am. J. Physiol. Endocrinol. Metab. 285, E433–E437 (2003).

    Article  CAS  PubMed  Google Scholar 

  42. Starkie, R., Ostrowski, S. R., Jauffred, S., Febbraio, M. & Pedersen, B. K. Exercise and IL-6 infusion inhibit endotoxin-induced TNF-α production in humans. FASEB J. 17, 884–886 (2003).

    Article  CAS  PubMed  Google Scholar 

  43. Freeman, B. D. & Buchman, T. G. Interleukin-1 receptor antagonist as therapy for inflammatory disorders. Expert Opin. Biol. Ther. 1, 301–308 (2001).

    Article  CAS  PubMed  Google Scholar 

  44. Maynard, C. L. & Weaver, C. T. Diversity in the contribution of IL-10 to cell-mediated immune regulation. Immunol. Rev. 226, 219–233 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Moore, K. W., de Waal Malefyt, R., Coffman, R. L. & O'Garra, A. Interleukin-10 and the interleukin-10 receptor. Annu. Rev. Immunol. 19, 683–765 (2001).

    Article  CAS  PubMed  Google Scholar 

  46. Hong, E. G. et al. Interleukin-10 prevents diet-induced insulin resistance by attenuating macrophage and cytokine response in skeletal muscle. Diabetes 58, 2525–2535 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Miyashita, M., Burns, S. F. & Stensel, D. J. Accumulating short bouts of brisk walking reduces postprandial plasma triacylglycerol concentrations and resting blood pressure in healthy young men. Am. J. Clin. Nutr. 88, 1225–1231 (2008).

    CAS  PubMed  Google Scholar 

  48. Murphy, M., Nevill, A., Neville, C., Biddle, S. & Hardman, A. E. Accumulating brisk walking for fitness, cardiovascular risk, and psychological health. Med. Sci. Sports Exerc. 34, 1468–1474 (2002).

    Article  PubMed  Google Scholar 

  49. Galbo, H. Hormonal and Metabolic Adaptation to Exercise (Georg Thieme Verlag, Stuttgart, 1983).

    Google Scholar 

  50. Cupps, T. R. & Fauci, A. S. Corticosteroid-mediated immunoregulation in man. Immunol. Rev. 65, 133–155 (1982).

    Article  CAS  PubMed  Google Scholar 

  51. Bergmann, M. et al. Attenuation of catecholamine-induced immunosuppression in whole blood from patients with sepsis. Shock 12, 421–427 (1999).

    Article  CAS  PubMed  Google Scholar 

  52. Jiao, P. et al. Obesity-related upregulation of monocyte chemotactic factors in adipocytes: involvement of nuclear factor-κB and c-Jun NH2-terminal kinase pathways. Diabetes 58, 104–115 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Kim, D. H. et al. The role of GM-CSF in adipose tissue inflammation. Am. J. Physiol. Endocrinol. Metab. 295, E1038–E1046 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Kanda, H. et al. MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J. Clin. Invest. 116, 1494–1505 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Xu, H. et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J. Clin. Invest. 112, 1821–1830 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Gautier, E. L., Jakubzizk, C. & Randolph, G. J. Regulation of the migration and survival of monocytes subsets by chemokine receptors and its relevance to atheroscelorosis. Arterioscler. Thromb. Vasc. Biol. 29, 1412–1418 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Zeyda, M., Huber, J., Prager, G. & Stulnig, T. M. Inflammation correlates with markers of T-cell subsets including regulatory T cells in adipose tissue from obese patients. Obesity 19, 743–748 (2011).

    Article  CAS  PubMed  Google Scholar 

  58. Cinti, S. et al. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J. Lipid Res. 46, 2347–2355 (2005).

    Article  CAS  PubMed  Google Scholar 

  59. Bruun, J. M., Lihn, A. S., Pedersen, S. B. & Richelsen, B. Monocyte chemoattractant protein-1 release is higher in visceral than subcutaneous human adipose tissue (AT): implication of macrophages resident in the AT. J. Clin. Endocrinol. Metab. 90, 2282–2289 (2005).

    Article  CAS  PubMed  Google Scholar 

  60. Bishop, N. C., Walker, G. J., Gleeson, M., Wallace, F. A. & Hewitt, C. R. A. Human T lymphocyte migration towards the supernatants of human rhinovirus infected airway epithelial cells: influence of exercise and carbohydrate intake. Exerc. Immunol. Rev. 15, 42–59 (2009).

    Google Scholar 

  61. Bermon, S. Airway inflammation and upper respiratory tract infection in athletes: is there a link? Exerc. Immunol. Rev. 13, 6–14 (2007).

    PubMed  Google Scholar 

  62. Maffei, M. et al. The obesity and inflammatory marker haptoglobin attracts monocytes via interaction with chemokine (C-C motif) receptor 2 (CCR2). BMC Biol. 17, 87 (2009).

    Article  CAS  Google Scholar 

  63. Nara, N. et al. Disruption of CXC motif chemokine ligand-14 in mice ameliorates obesity-induced insulin resistance. J. Biol. Chem. 282, 30794–30803 (2007).

    Article  CAS  PubMed  Google Scholar 

  64. Bosanská, L. et al. The influence of obesity and different fat depots on adipose tissue gene expression and protein levels of cell adhesion molecules. Physiol. Res. 59, 79–88 (2010).

    PubMed  Google Scholar 

  65. Chow, F. Y., Nikolic-Paterson, D. J., Ozols, E., Atkins, R. C. & Tesch, G. H. Intercellular adhesion molecule-1 deficiency is protective against nephropathy in type 2 diabetic db/db mice. J. Am. Soc. Nephrol. 16, 1711–1722 (2005).

    Article  CAS  PubMed  Google Scholar 

  66. Zoppini, G. et al. Effects of moderate-intensity exercise training on plasma biomarkers of inflammation and endothelial dysfunction in older patients with type 2 diabetes. Nutr. Metab. Cardiovasc. Dis. 16, 543–549 (2006).

    Article  CAS  PubMed  Google Scholar 

  67. Martinez, F. O., Sica, A., Mantovani, A. & Locati, M. Macrophage activation and polarization. Front. Biosci. 13, 453–461 (2008).

    CAS  Google Scholar 

  68. Lumeng, C. N., Bodzin, J. L. & Saltiel, A. R. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J. Clin. Invest. 117, 175–184 (2007). This study demonstrates that obesity leads to a shift in adipose tissue macrophage polarization from an alternatively activated state to a classically activated (more pro-inflammatory) state.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Kaisho, T. & Akira, S. Toll-like receptor function and signalling. J. Allergy Clin. Immunol. 117, 979–987 (2006).

    Article  CAS  PubMed  Google Scholar 

  70. Takeda, K., Kaisho, T. & Akira, S. S. Toll-like receptors. Annu. Rev. Immunol. 21, 335–376 (2003).

    Article  CAS  PubMed  Google Scholar 

  71. Lancaster, G. I. et al. The physiological regulation of Toll-like receptor expression and function in humans. J. Physiol. 563, 945–955 (2005). This was the first study to show that acute exercise causes a downregulation of TLR expression on circulating monocytes and their downstream functional responses.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Oliveira, M. & Gleeson, M. The influence of prolonged cycling on monocyte Toll-like receptor 2 and 4 expression in healthy men. Eur. J. Appl. Physiol. 109, 251–257 (2010).

    Article  CAS  PubMed  Google Scholar 

  73. Stewart, L. K. et al. Influence of exercise training and age on CD14+ cell surface expression of Toll-like receptor 2 and 4. Brain Behav. Immunol. 19, 389–397 (2005). This paper reports that exercise training is associated with a reduction in TLR expression on circulating monocytes in humans.

    Article  CAS  Google Scholar 

  74. Nguyen, M. T. et al. A subpopulation of macrophages infiltrates hypertrophic adipose tissue and is activated by free fatty acids via Toll-like receptors 2 and 4 and JNK-dependent pathways. J. Biol. Chem. 282, 35279–35292 (2007).

    Article  CAS  PubMed  Google Scholar 

  75. Starkie, R., Ostrowski, S. R., Jauffred, S., Febbraio, M. & Pedersen, B. K. Exercise and IL-6 infusion inhibit endotoxin-induced TNF-α production in humans. FASEB J. 17, 884–886 (2003).

    Article  CAS  PubMed  Google Scholar 

  76. Skinner, N. A., MacIsaac, C. M., Hamilton, J. A. & Visvanathan, K. Regulation of Toll-like receptor (TLR)2 and TLR4 on CD14dimCD16+ monocytes in response to sepsis-related antigens. Clin. Exp. Immunol. 141, 270–278 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Belge, K. U. et al. The proinflammatory CD14+CD16+DR++ monocytes are a major source of TNF. J. Immunol. 168, 3536–3542 (2002).

    Article  CAS  PubMed  Google Scholar 

  78. Baeten, D. et al. Human cartilage gp39+, CD16+ monocytes in peripheral blood and synovium: correlation with joint destruction in rheumatoid arthritis. Arthritis Rheum. 43, 1233–1243 (2000).

    Article  CAS  PubMed  Google Scholar 

  79. Schlitt, A. et al. CD14+CD16+ monocytes in coronary artery disease and their relationship to serum TNF-α levels. Thromb. Haemost. 92, 419–424 (2004).

    Article  CAS  PubMed  Google Scholar 

  80. Giulietti, A. et al. Monocytes from type 2 diabetic patients have a pro-inflammatory profile: 1,25-dihydroxyvitamin D3 works as anti-inflammatory. Diabetes Res. Clin. Pract. 77, 47–57 (2007).

    Article  CAS  PubMed  Google Scholar 

  81. Simpson, R. J. et al. Toll-like receptor expression on classic and pro-inflammatory blood monocytes after acute exercise in humans. Brain Behav. Immunol. 23, 232–239 (2009).

    Article  CAS  Google Scholar 

  82. Fingerle-Rowson, G., Angstwurm, M., Andreesen, R. & Ziegler-Heitbrock, H. W. Selective depletion of CD14+CD16+ monocytes by glucocorticoid therapy. Clin. Exp. Immunol. 112, 501–506 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Viswanathan, K. & Dhabhar, F. S. Stress-induced enhancement of leukocyte trafficking into sites of surgery or immune activation. Proc. Natl Acad. Sci. USA 102, 5808–5813 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Keylock, K. T. et al. Exercise accelerates cutaneous wound healing and decreases wound inflammation in aged mice. Am. J. Physiol. 294, R179–R184 (2008).

    CAS  Google Scholar 

  85. Sakaguchi, S. Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nature Immunol. 6, 345–352 (2005).

    Article  CAS  Google Scholar 

  86. Fernandez, M. A. et al. T regulatory cells contribute to the attenuated primary CD8+ and CD4+ T cell responses to herpes simplex virus type 2 in neonatal mice. J. Immunol. 180, 1556–1564 (2008).

    Article  CAS  PubMed  Google Scholar 

  87. Furuichi, Y. et al. Depletion of CD25+CD4+ T cells (Tregs) enhances the HBV-specific CD8+ T cell response primed by DNA immunization. World J. Gastroenterol. 11, 3772–3777 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  88. Nakahara, M. et al. The effect of regulatory T-cell depletion on the spectrum of organ-specific autoimmune diseases in nonobese diabetic mice at different ages. Autoimmunity 9 Feb 2011 (doi:10.3109/08916934.2010.548839).

    Article  CAS  PubMed  Google Scholar 

  89. Paust, H. J. et al. Regulatory T cells control the Th1 immune response in murine crescentic glomerulonephritis. Kidney Int. 80, 154–164 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Yeh, S. H. et al. Regular Tai Chi Chuan exercise improves T cell helper function of patients with type 2 diabetes mellitus with an increase in T-bet transcription factor and IL-12 production. Br. J. Sports Med. 43, 845–850 (2009).

    Article  PubMed  Google Scholar 

  91. Balducci, S. et al. Effect of an intensive exercise intervention strategy on modifiable cardiovascular risk factors in subjects with type 2 diabetes mellitus: a randomized controlled trial: the Italian Diabetes and Exercise Study (IDES). Arch. Intern. Med. 170, 1794–1803 (2010).

    Article  PubMed  Google Scholar 

  92. Pedersen, B. K. & Hoffman-Goetz, L. Exercise and the immune system: regulation, integration, and adaptation. Physiol. Rev. 80, 1055–1081 (2000).

    Article  CAS  PubMed  Google Scholar 

  93. Matthews, C. E. et al. Moderate to vigorous physical activity and risk of upper-respiratory tract infection. Med. Sci. Sports Exerc. 34, 1242–1248 (2002).

    Article  PubMed  Google Scholar 

  94. Nieman, D. C., Henson, D. A., Austin, M. D. & Sha, W. Upper respiratory tract infection is reduced in physically fit and active adults. Br. J. Sports Med. 1 Nov 2010 (doi:10.1136/bjsm.2010.077875). References 93 and 94 show that regular moderate exercise reduces the incidence of upper respiratory tract infections in humans.

    Article  PubMed  Google Scholar 

  95. Bishop, N. C. in Immune Function in Sport and Exercise (ed. Gleeson, M.) 1–14 (Elsevier, Edinburgh, 2005).

    Google Scholar 

  96. Fahlman, M. M. & Engels, H. J. Mucosal IgA and URTI in American college football players: a year longitudinal study. Med. Sci. Sports Exerc. 37, 374–380 (2005).

    Article  CAS  PubMed  Google Scholar 

  97. Nieman, D. C., Johanssen, L. M., Lee, I. W. & Arabatzis, K. Infectious episodes in runners before and after the Los Angeles marathon. J. Sports Med. Phys. Fitness 30, 316–328 (1990).

    CAS  PubMed  Google Scholar 

  98. Gleeson, M. Exercise and immune function. J. Appl. Physiol. 103, 693–699 (2007).

    Article  CAS  PubMed  Google Scholar 

  99. Gleeson, M. et al. Respiratory infection risk in athletes: association with antigen-stimulated IL-10 production and salivary IgA secretion. Scand. J. Med. Sci. Sports 8 Mar 2011 (doi:10.1111/j.1600-0838.2010.01272.x). This study showed that illness-prone athletes had higher levels of IL-10 production in whole blood culture in response to ex vivo antigen stimulation.

    Article  Google Scholar 

  100. van der Sluijs, K. F. IL-10 is an important mediator of the enhanced susceptibility to pneumococcal pneumonia after influenza infection. J. Immunol. 172, 7603–7609 (2004).

    Article  CAS  PubMed  Google Scholar 

  101. Blackburn, S. D. & Wherry, E. J. IL-10, T cell exhaustion and viral persistence. Trends Microbiol. 15, 143–146 (2007).

    Article  CAS  PubMed  Google Scholar 

  102. Thune, I. & Furberg, A. S. Physical activity and cancer risk: dose–response and cancer, all sites and site-specific. Med. Sci. Sports Exerc. 33, S530–S550 (2001).

    Article  CAS  PubMed  Google Scholar 

  103. Gill, J. M. R. & Cooper, A. R. Physical activity and prevention of type 2 diabetes mellitus. Sports Med. 38, 807–824 (2008).

    Article  PubMed  Google Scholar 

  104. Tuomilehto, J. et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N. Engl. J. Med. 344, 1343–1350 (2001).

    Article  CAS  PubMed  Google Scholar 

  105. Eriksson, K. F. & Lindgärde, F. Prevalence of type 2 (non-insulin dependent) diabetes mellitus by diet and physical exercise: the 6-year Malmö feasibility study. Diabetologia 34, 891–898 (1991).

    Article  CAS  PubMed  Google Scholar 

  106. Church, T. S. et al. Exercise capacity and body composition as predictors of mortality among men with diabetes. Diabetes Care 27, 83–88 (2004).

    Article  PubMed  Google Scholar 

  107. Tanasescu, M., Leitzmann, M. F., Rimm, E. B. & Hu, F. B. Physical activity in relation to cardiovascular disease and total mortality among men with type 2 diabetes. Circulation 107, 2435–2439 (2003).

    Article  PubMed  Google Scholar 

  108. Donath, M. Y. & Shoelson, S. E. Type 2 diabetes as an inflammatory disease. Nature Rev. Immunol. 11, 98–107 (2011).

    Article  CAS  Google Scholar 

  109. Tanasescu, M. et al. Exercise type and intensity in relation to coronary heart disease in men. JAMA 288, 1994–2000 (2002).

    Article  PubMed  Google Scholar 

  110. Eliassen, H. A., Hankinson, S. E., Rosner, B., Holmes, M. D. & Willet, W. C. Physical activity and risk of breast cancer among postmenopausal women. Archiv. Int. Med. 170, 1758–1764 (2010).

    Article  Google Scholar 

  111. Wolin, K. Y., Yan, Y. & Colditz, G. A. Physical activity and risk of colon adenoma: a meta-analysis. Br. J. Cancer 104, 882–885 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Abbott, R. D. et al. Walking and dementia in physically capable elderly men. JAMA 292, 1447–1453 (2004).

    Article  CAS  PubMed  Google Scholar 

  113. Bishop, N. C. & Gleeson, M. Acute and chronic effects of exercise on markers of mucosal immunity. Front. Biosci. 14, 4444–4456 (2009).

    Article  CAS  Google Scholar 

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Glossary

Type 2 diabetes mellitus

A disorder of glucose homeostasis that is characterized by inappropriately increased blood glucose levels and resistance of tissues to the action of insulin. Recent studies indicate that inflammation in adipose tissue, liver and muscle contributes to the insulin-resistant state that is characteristic of type 2 diabetes mellitus, and that the anti-diabetic actions of peroxisome proliferator-activated receptor-γ agonists result, in part, from their anti-inflammatory effects in these tissues.

Immunometabolism

This term has been recently introduced to describe the multilevel interactions between the metabolic and immune systems.

Adipokines

Factors, including cytokines, that are secreted from adipose tissue. Some adipokines promote inflammatory responses and metabolic dysfunction, whereas others have anti-inflammatory functions and beneficial effects on metabolic disorders.

Insulin resistance

A condition characterized by the inability of cells in the muscle, liver and adipose tissue to respond appropriately to endogenous insulin, resulting in increased blood glucose levels.

Triglycerides

The storage form of fat found in adipose tissue.

Low-density lipoprotein

(LDL). A protein–lipid complex in the blood plasma that facilitates the transport of triglycerides, cholesterol and phospholipids. High blood levels of LDL are associated with an increased risk of coronary heart disease.

High-density lipoprotein

(HDL). A protein–lipid complex in the blood plasma that facilitates the transport of triglycerides, cholesterol and phospholipids. High blood levels of HDL are associated with a decreased risk of coronary heart disease.

Regulatory T cells

(TReg cells). A specialized subpopulation of T cells that acts to suppress activation of the immune system and thereby maintains immune system homeostasis and tolerance to self antigens. These cells are involved in shutting down immune responses after they have successfully tackled invading microorganisms, and also in regulating immune responses that may potentially attack one's own tissues (autoimmunity).

Leptin

A regulatory hormone that is produced by adipocytes. When released into the circulation, it influences the hypothalamus to control appetite, and its production correlates with the amount of adipose tissue.

Adiponectin

A cytokine released from adipocytes that has anti-inflammatory effects and acts as an insulin sensitizer.

Cortisol

A steroid hormone secreted from the adrenal cortex in response to stress that has anti-inflammatory as well as catabolic effects.

Adrenaline

A catecholamine secreted from the adrenal medulla in response to stress that has effects on the cardiovascular system (for example, increased heart rate and peripheral vasoconstriction) and on metabolism (for example, increased glycogen breakdown and lipolysis). It also has some immunosuppressive effects (for example, decreased pro-inflammatory cytokine production by monocytes and lymphocytes).

Hypothalamic–pituitary–adrenal axis

A major component of the stress system that consists of the paraventricular nucleus (PVN) of the hypothalamus, the anterior pituitary gland and the adrenal cortices. Corticotropin-releasing hormone and vasopressin secreted by PVN neurons into the hypophyseal portal system stimulate pituitary cells to produce and secrete adrenocorticotropic hormone (ACTH) into the general circulation. ACTH then stimulates cortisol secretion by the adrenal glands.

Sympathetic nervous system

A part of the nervous system that serves to accelerate the heart rate, constrict blood vessels, raise blood pressure and mobilize metabolic fuels. It is responsible for the 'fight-or-flight response' to stress and physical activity (that is, the non-volitional preparation of the organism for emergency situations).

Adrenocorticotropic hormone

A peptide hormone secreted from the anterior pituitary gland that stimulates the release of cortisol from the adrenal glands.

Noradrenaline

A catecholamine secreted from sympathetic nerve endings that has effects on the cardiovascular system (for example, increased heart rate and peripheral vasoconstriction) and on metabolism (for example, increased glycogen breakdown and lipolysis). It also has some immunosuppressive effects (for example, decreased pro-inflammatory cytokine production by monocytes and lymphocytes).

M1-type macrophages

Macrophages that are activated in the presence of TH1-type cytokines, such as interferon-γ, and produce, among other molecules, inducible nitric oxide synthase and nitric oxide.

M2-type macrophages

Macrophages that are activated in the presence of TH2-type cytokines, such as interleukin-4 (IL-4) or IL-13, and express arginase 1, the mannose receptor CD206 and the IL-4 receptor α-chain.

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Gleeson, M., Bishop, N., Stensel, D. et al. The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. Nat Rev Immunol 11, 607–615 (2011). https://doi.org/10.1038/nri3041

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