Increased Circulating Anti-inflammatory Cells in Marathon-trained Runners

Abstract

Exercise training can alter immune function. Marathon training has been associated with an increased susceptibility to infectious diseases and an increased activity of inflammatory-based diseases, but the precise mechanisms are unknown. The purpose of this study was to compare levels of circulating CD4 ⁺  T cell subsets in the periphery of marathon-trained runners and matched non-marathon controls. 19 recreational marathoners that were 4 weeks from running a marathon and 19 demographically-matched healthy control subjects had the percentage of CD4 ⁺  T cell subpopulations (T helper 1, T helper 2, T helper 1/T helper 2 ratio, regulatory T cells, CD4⁺IL10⁺, and CD4⁺TGFβ⁺ (Transforming Growth Factor-beta) measured by flow cytometry. Marathon-trained runners had significantly less T helper 1 and regulatory T cells and significantly more T helper 2, CD4 ⁺ IL10 ⁺ , and TGFβ ⁺  cells than the control subjects. The alterations in the percentage of T helper 1 and T helper 2 cells led to a significantly lower T helper 1/T helper 2 ratio in the marathon-trained runners. These data suggest that endurance-based training can increase the number of anti-inflammatory cells. This may be a potential mechanism for the increased incidence of both infectious and inflammatory diseases observed in endurance athletes.

Keywords

immunology - T cell - cytokine - intracellular cytokine staining

• References

• 1 Agarwal SK, Marshall Jr GD. Glucocorticoid-induced type 1/type 2 cytokine alterations in humans: a model for stress-related immune dysfunction. J Interferon Cytokine Res 1998; 18: 1059-1068
• 2 Allan SE, Broady R, Gregori S, Himmel ME, Locke N, Roncarolo MG, Bacchetta R, Levings MK. CD4+ T-regulatory cells: toward therapy for human diseases. Immunol Rev 2008; 223: 391-421
• 3 Baum M, Muller-Steinhardt M, Liesen H, Kirchner H. Moderate and exhaustive endurance exercise influences the interferon-gamma levels in whole-blood culture supernatants. Eur J Appl Physiol 1997; 76: 165-169
• 4 Bretscher PA. On the mechanism determining the TH1/TH2 phenotype of an immune response, and its pertinence to strategies for the prevention, and treatment, of certain infectious diseases. Scand J Immunol 2014; 79: 361-376
• 5 Czarkowska-Paczek B, Bartlomiejczyk I, Przybylski J. The serum levels of growth factors: PDGF, TGF-beta and VEGF are increased after strenuous physical exercise. J Physiol Pharmacol 2006; 57: 189-197
• 6 Fu H, Yu P. The effect of aerobic exercise on serum IL-4 and TNF-alpha of patients with allergic rhinitis. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2013; 27: 1321-1323
• 7 Gabrysova L, Howes A, Saraiva M, O'Garra A. The regulation of IL-10 expression. Curr Top Microbiol Immunol 2014; 380: 157-190
• 8 Garcia-Aymerich J, Varraso R, Danaei G, Camargo Jr CA, Hernan MA. Incidence of adult-onset asthma after hypothetical interventions on body mass index and physical activity: an application of the parametric g-formula. Am J Epidemiol 2014; 179: 20-26
• 9 Gleeson M. Immune system adaptation in elite athletes. Curr Opin Clin Nutr Metab Care 2006; 9: 659-665
• 10 Gleeson M, Bishop N, Oliveira M, Tauler P. Influence of training load on upper respiratory tract infection incidence and antigen-stimulated cytokine production. Scand J Med Sci Sports 2013; 23: 451-457
• 11 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. Eur J Appl Physiol 2013; 113: 1839-1848
• 12 Harriss DJ, Atkinson G. Ethical standards in sport and exercise science research: 2014 update. Int J Sports Med 2013; 34: 1025-1028
• 13 Hausswirth C, Louis J, Aubry A, Bonnet G, Duffield R, LE Meur Y. Evidence of disturbed sleep and increased illness in overreached endurance athletes. Med Sci Sports Exerc 2014; 46: 1036-1045
• 14 Lancaster GI, Khan Q, Drysdale PT, Wallace F, Jeukendrup AE, Drayson MT, Gleeson M. Effect of prolonged exercise and carbohydrate ingestion on type 1 and type 2 T lymphocyte distribution and intracellular cytokine production in humans. J Appl Physiol 2005; 98: 565-571
• 15 Lang PO, Govind S, Bokum AT, Kenny N, Matas E, Pitts D, Aspinall R. Immune senescence and vaccination in the elderly. Curr Top Med Chem 2013; 13: 2541-2550
• 16 Marshall Jr GD, Agarwal SK, Lloyd C, Cohen L, Henninger EM, Morris GJ. Cytokine dysregulation associated with exam stress in healthy medical students. Brain Behav Immun 1998; 12: 297-307
• 17 Matthews CE, Ockene IS, Freedson PS, Rosal MC, Merriam PA, Hebert JR. Moderate to vigorous physical activity and risk of upper-respiratory tract infection. Med Sci Sports Exerc 2002; 34: 1242-1248
• 18 Maue AC, Haynes L. CD4+ T cells and immunosenescence – a mini-review. Gerontology 2009; 55: 491-495
• 19 Moyna NM, Acker GR, Fulton JR, Weber K, Goss FL, Robertson RJ, Tollerud DJ, Rabin BS. Lymphocyte function and cytokine production during incremental exercise in active and sedentary males and females. Int J Sports Med 1996; 17: 585-591
• 20 Nieman DC, Johanssen LM, Lee JW, Arabatzis K. Infectious episodes in runners before and after the Los Angeles Marathon. J Sports Med Phys Fitness 1990; 30: 316-328
• 21 Pedersen L, Elers J, Backer V. Asthma in elite athletes: pathogenesis, diagnosis, differential diagnoses, and treatment. Phys Sportsmed 2011; 39: 163-171
• 22 Perry C, Pick M, Bdolach N, Hazan-Halevi I, Kay S, Berr I, Reches A, Harishanu Y, Grisaru D. Endurance exercise diverts the balance between Th17 cells and regulatory T cells. PloS one 2013; 8: e74722
• 23 Rehm KE, Elci OU, Hahn K, Marshall Jr GD. The impact of self-reported psychological stress levels on changes to peripheral blood immune biomarkers in recreational marathon runners during training and recovery. Neuroimmunomodulation 2013; 20: 164-176
• 24 Robson-Ansley P, Howatson G, Tallent J, Mitcheson K, Walshe I, Toms C, DU Toit G, Smith M, Ansley L. Prevalence of allergy and upper respiratory tract symptoms in runners of the London marathon. Med Sci Sports Exerc 2012; 44: 999-1004
• 25 Sakaguchi S, Wing K, Onishi Y, Prieto-Martin P, Yamaguchi T. Regulatory T cells: how do they suppress immune responses?. Int Immunol 2009; 21: 1105-1111
• 26 Salicru AN, Sams CF, Marshall GD. Cooperative effects of corticosteroids and catecholamines upon immune deviation of the type-1/type-2 cytokine balance in favor of type-2 expression in human peripheral blood mononuclear cells. Brain Behav Immun 2007; 21: 913-920
• 27 Schroder K, Hertzog PJ, Ravasi T, Hume DA. Interferon-gamma: an overview of signals, mechanisms and functions. J Leukoc Biol 2004; 75: 163-189
• 28 Skoluda N, Dettenborn L, Stalder T, Kirschbaum C. Elevated hair cortisol concentrations in endurance athletes. Psychoneuroendocrinology 2012; 37: 611-617
• 29 Sokol CL, Barton GM, Farr AG, Medzhitov R. A mechanism for the initiation of allergen-induced T helper type 2 responses. Nat Immunol 2008; 9: 310-318
• 30 Steensberg A, Toft AD, Bruunsgaard H, Sandmand M, Halkjaer-Kristensen J, Pedersen BK. Strenuous exercise decreases the percentage of type 1 T cells in the circulation. J Appl Physiol 2001; 91: 1708-1712
• 31 Taylor A, Verhagen J, Blaser K, Akdis M, Akdis CA. Mechanisms of immune suppression by interleukin-10 and transforming growth factor-beta: the role of T regulatory cells. Immunology 2006; 117: 433-442
• 32 Walsh NP, Gleeson M, Shephard RJ, Gleeson M, Woods JA, Bishop NC, Fleshner M, Green C, Pedersen BK, Hoffman-Goetz L, Rogers CJ, Northoff H, Abbasi A, Simon P. Position statement. Part one: Immune function and exercise. Exerc Immunol Rev 2011; 17: 6-63
• 33 Wilson LD, Zaldivar FP, Schwindt CD, Wang-Rodriguez J, Cooper DM. Circulating T-regulatory cells, exercise and the elite adolescent swimmer. Pediatr Exerc Sci 2009; 21: 305-317
• 34 Xiang L, Marshall Jr GD. Immunomodulatory effects of in vitro stress hormones on FoxP3, Th1/Th2 cytokine and costimulatory molecule mRNA expression in human peripheral blood mononuclear cells. Neuroimmunomodulation 2011; 18: 1-10
• 35 Xiang L, Marshall Jr GD. Immunomodulatory effects of dexamethasone on gene expression of cytokine and stress hormone receptors in peripheral blood mononuclear cells. Int Immunopharmacol 2013; 17: 556-560
• 36 Yeh SH, Chuang H, Lin LW, Hsiao CY, Eng HL. Regular tai chi chuan exercise enhances functional mobility and CD4CD25 regulatory T cells. Br J Sports Med 2006; 40: 239-243
• 37 Yu N, Li X, Song W, Li D, Yu D, Zeng X, Li M, Leng X, Li X. CD4(+)CD25 (+)CD127 (low/−) T cells: a more specific Treg population in human peripheral blood. Inflammation 2012; 35: 1773-1780