Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Sports Medicine
Published in: Sports Medicine 5/2003

01-04-2003 | Review Article

Overtraining, Excessive Exercise, and Altered Immunity

Is This a T Helper-1 Versus T Helper-2 Lymphocyte Response?

Author: Lucille Lakier Smith

Published in: Sports Medicine | Issue 5/2003

Login to get access

Abstract

Overtraining syndrome (OTS) occurs where an athlete is training vigorously, yet performance deteriorates. One sign of OTS is suppressed immune function, with an increased incidence of upper respiratory tract infection (URTI). An increased incidence of URTIs is also associated with high volume/intensity training, as well as with excessive exercise (EE), such as a marathon, manifesting between 3–72 hours post-race. Presently, there is no encompassing theory to explain EE and altered immune competence. Recently, it has been conclusively established that T helper lymphocytes (TH), a crucial aspect of immune function, represent two distinct functional subsets: TH1 and TH2 lymphocytes. TH1 lymphocytes are associated with cell-mediated immunity (CMI) and the killing of intracellular pathogens, while TH2 lymphocytes are associated with humoral immunity and antibody production. When TH-precursor cells are activated, the balance is tipped in favour of one or the other. Furthermore, the most appropriate means of determining the TH-subset, is by the prevailing cytokine ‘pattern’. This paper hypothesises that exercise-related immunosuppression is due to tissue trauma sustained during intense exercise, producing cytokines, which drive the development of a TH2 lymphocyte profile. A TH2 cell response results in simultaneous suppression of CMI, rendering the athlete susceptible to infection. Additionally, increased levels of circulating stress hormones (cortisol and catecholamines), as well as prostaglandin E2, support up-regulation of TH2 lymphocytes. Marathon-related data are presented to support this hypothesis. It is concluded that an increased incidence of illness associated with OTS and in response to EE is not due to immunosuppression per se, but rather to an altered focus of immune function, with an up-regulation of humoral immunity and suppression of CMI.
Literature
1.
Lehmann M, Foster C, Keul J. Overtraining in endurance athletes: a brief review. Med Sci Sports Exerc 1993; 25(7): 854–62PubMed
2.
Mackinnon LT. Chronic exercise training effects on immune function. Med Sci Sports Exerc 2000; 32(7): S369–76PubMed
3.
Nieman DC. Exercise, infection, and immunity. Int J Sports Med 1994; 15: S131–41PubMed
4.
Pedersen BK, Rohde T, Zacho M. Immunity in athletes. J Sports Med Phys Fitness 1996; 36(4): 236–45PubMed
5.
Peters E, Bateman E. Ultra-marathon running and upper respiratory tract infections: an epidemiiological survey. S Afr Med J 1983; 64: 582–4PubMed
6.
Sharp NCC, Koutedakis Y. Sport and the overtraining syndrome: immunological aspects. Br Med Bull 1992; 48(3): 518–33PubMed
7.
Shepherd RJ. Physical activity, training, and the immune response. Carmel (IN): Cooper Publishing Group, 1997
8.
MacKinnon LT. Advances in exercise immunology. Champaign (IL): Human Kinetics, 1999
9.
MacKinnon LT. Special feature for the Olympics: effects of exercise on the immune system: overtraining effects on immunity and performance in athletes. Immunol Cell Biol 2000; 78(5): 502–9PubMed
10.
Fry RW, Morton AR, Keast D. Overtraining in athletes: an update. Sports Med 1991; 12: 32–65PubMed
11.
Fry AC, Kraemer WJ. Resistance exercise overtraining and overreaching. Sports Med 1997; 23(2): 106–29PubMed
12.
Kuipers H, Keizer HA. Overtraining in elite athletes: review and directions for the future. Sports Med 1988; 6: 79–92PubMed
13.
Noakes T. Lore of running. Cape Town: Oxford University Press, 2001: 639–78
14.
Stone MH, Keith RE, Kearney JT, et al. Overtraining: a review of the signs, symptoms and possible causes. J Appl Sport Sci Res 1991; 5(1): 35–50
15.
O’Toole M. Overreaching and overtraining in endurance athletes. In: Kreider RB, Fry AC, O’Toole ML, editors. Overtraining in sport. Champaign (IL): Human Kinetics, 1998: 3–18
16.
Smith LL. Cytokine hypothesis of overtraining: a physiological adaptation to excessive stress? Med Sci Sports Exerc 2000; 32(2): 317–31PubMed
17.
Fry AC. The role of training intensity in resistance exercise: overtraining and overreacahing. In: Kreider RB, Fry AC, O’Toole ML, editors. Overtraining in sports. Champaign (IL): Human Kinetics Publishers Inc, 1998: 107–30
18.
Costill DL, Flynn MG, Kirwan JP, et al. Effects of repeated days of intensified training on muscle glycogen and swimming performance. Med Sci Sports Exerc 1988; 20: 249–54PubMed
19.
Keizer HA. Neuroendocrine aspects of overtraining. In: Kreider RB, Fry AC, O’Toole ML, editors. Overtraining in sport. Champaign (IL): Human Kinetics Publishers Inc, 1998: 145–68
20.
Kreider RB. Central fatigue hypothesis and overtraining. In: Kreider RB, Fry AC, O’Toole ML, editors. Overtraining in sport. Champaign (IL): Human Kinetics Publishers Inc., 1998: 309–34
21.
Newsholme EA, Parry-Billings M, McAndrew N, et al. A biochemical mechanism to explain some characteristics of overtraining. In: Brouns F, editor. Advances in nutrition and team sport. Basel: Karger, 1991: 79–83
22.
Sevier TL. Infectious disease in athletes. Med Clin North Am 1994; 78(2): 389–412PubMed
23.
Muns G, Singer P, Wolf F, et al. Impaired nasal mucociliary clearance in long-distance runners. Int J Sports Med 1995; 16: 209–13PubMed
24.
Nieman DC. Prolonged aerobic exercise, immune response, and risk of infection. In: Hoffman-Goetz L, editor. Exercise and immune function. Boca Raton (FL): CRC Press, 1996: 143–61
25.
Newsholme EA. Biochemical mechanisms to explain immunosuppression in well-trained and overtrained athletes. Int J Sports Med 1994; 15: S142–7PubMed
26.
Nieman D. Is infection risk linked to exercise workload? Med Sci Sports Exerc 2000; 32(7): S396–495
27.
Pedersen BK, editor. Exercise immunology. New York (NY): Chapman & Hall, 1997
28.
Pedersen BK, Bruunsgaard H, Jensen M, et al. Exercise and the immune system: influence of nutrition and ageing. J Sci Med Sport 1999; 2(3): 234–52PubMed
29.
Weidner TG. Upper respiratory illness and sport and exercise. Int J Sports Med 1994; 15: 1–9PubMed
30.
Gannon GA, Shek PN, Shephard RJ. Natural killer cells: modulation by intensity and duration of exercise. Exerc Immunol Rev 1995; 1: 26–48
31.
Muns G. Effect of long-distance running on polymorphonuclear neutrophil phagocytic function of the upper airways. Int J Sports Med 1993; 15: 96–9
32.
Suzuki K, Yamada M, Kurakake S, et al. Circulating cytokines and hormones with immunosuppressive but neutrophil-priming potentials rise after endurance exercise in humans. Eur J Appl Physiol 2000; 81(4): 281–7PubMed
33.
Gabriel HHW, Urhausen A, Valet G, et al. Overtraining and immune system: a propective longitudinal study in endurance athletes. Med Sci Sports Exerc 1998; 30(7): 1151–7PubMed
34.
Field CJ, Johnson I, Pratt VC. Glutamine and arginine: immunonutrients for improved health. Med Sci Sports Exerc 2000; 32(7): S377–88PubMed
35.
Bishop NC, Blannin AK, Walsh NP, et al. Nutritional aspects of immunosuppression in athletes. Sports Med 1999; 28(3): 151–76PubMed
36.
Castell LM, Poortsmans JR, Leclercq R, et al. Some aspects of the acute phase response after a marathon race, and the effects of glutamine supplementaion. Eur J Appl Physiol Occup Phsyiol 1997; 75(1): 47–53
37.
Pedersen BK, Rohde T. Exercise, glutamine and the immune system. In: Pedersen BK, editor. Exercise immunology. New York: Chapman & Hall, 1997: 75–88
38.
Pedersen BK, Hoffman-Goetz L. Exercise and the immune system: regulation, integration, and adaptation. Physiol Rev 1999; 80(3): 1055–81
39.
Pedersen BK, Ullum H. NK cell response to physical activity: possible mechanisms of action. Med Sci Sports Exerc 1994; 26: 140–6PubMed
40.
Nieman DC, Pedersen BK. Exercise and immune function. Sports Med 1999; 27(2): 73–80PubMed
41.
Shepherd RJ, Shek PN. Effects of exercise and training on natural killer cell counts and cytolytic activity: a meta-analysis. Sports Med 1999; 28(3): 177–95
42.
Eichner ER. Overtraining: consequences and prevention. J Sports Sci 1995; 13: S41–8PubMed
43.
McKenzie DC. Markers of excessive exercise. Can J Appl Physiol 1999; 24(1): 66–73PubMed
44.
Northoff H, Sigrid E, Weinstock C. Exercise, injury and immune function. Exerc Immunol Rev 1995; 1: 1–25
45.
Hikida RS, Staron RS, Hagerman FC, et al. Muscle fiber necrosis associated with human marathon runners. J Neurol Sci 1983; 59: 185–202PubMed
46.
Pedersen BK, Ostrowski K, Rohde T, et al. The cytokine response to strenuous exercise. Can J Physiol Pharmacol 1998; 76: 505–11PubMed
47.
Taylor C, Rogers G, Goodman C, et al. Hematologic, iron-related, and acute-phase protein responses to sustained strenuous exercise. J Appl Physiol 1987; 62(2): 464–9PubMed
48.
Hartmann U, Mester J. Training and overtraining markers in selected sport events. Med Sci Sports Exerc 2000; 32(1): 209–15PubMed
49.
Warren GL, Lowe DA, Armstrong RB. Measurement tools used in the study of eccentric contraction-induced injury. Sports Med 1999; 27(1): 43–59PubMed
50.
Kibler WB, Chandler TJ. Musculoskeletal and orthopedic considerations. In: Kreider AF, Fry AC, O’Toole ML, editors. Overtraining in sport. Champaign (IL): Human Kinetics Publishers Inc, 1998: 169–92
51.
Seene T, Umnova M, Kaasik P. The exercise myopathy. In: Lehmann M, Foster C, Gastmann U, et al., editors. Overload, performance incompetance, and regeneration in sport. New York: Kluwer Academic/Plenum Publishers, 1999: 119–30
52.
Elenkov IJ, Chrousos GP. Stress hormones, Th1/Th2 patterns, pro/anti-inflammatory cytokines and susceptibility to disease. Trends Endocrinol Metab 1999; 10(9): 359–68PubMed
53.
Faist E, Schinkel C, Zimmer S. Update on the mechanisms of immune suppression of injury and immune modulation. World J Surg 1996; 20: 454–9PubMed
54.
Schaffer M, Barbul A. Lymphocyte function in wound healing and following injury. Br J Surgery1998; 85: 444–80
55.
Oberholzer A, Oberholzer C, Moldawer LL. Cytokine signaling: regulation of the immune response in normal and critically ill states. Crit Care Med 2000; 28 (4 Suppl.): N3–12PubMed
56.
Rhind SG, Shek PN, Shephard RJ. The impact of exercise on cytokines and receptor expression. Exerc Immunol Rev 1995; 1: 97–148
57.
Doherty DE, Downey GP, Worthen GS, et al. Monocyte retention and migration in pulmonary inflammation. Lab Invest 1988; 59: 200–12PubMed
58.
Willoughby DA, Moore AR, Colville-Nash PR, et al. Resolution of inflammation. Int J Immunopharmacol 2000; 22(12): 1131–5PubMed
59.
Buckley CD, Pilling D, Lord JM, et al. Fibroblasts regulate the switch from acute resolving to chronic persistent inflammation. Trends Immunol 2001; 22(4): 199–204PubMed
60.
Cannon JG. Inflammatory cytokines in nonpathological states. News Physiol Sci 2000; 15: 298–303PubMed
61.
Dinarello C. Role of pro- and anti-inflammatory cytokines during inflammation: experimental and clinical findings. J Biol Regul Homeost Agents 1997; 11: 91–103PubMed
62.
Elenkov IJ, Wilder RL, Chrousos GP, et al. The sympathetic nerve-an integrative interface between two supersystems: the brain and the immune system. Pharmacol Rev 2000; 52: 595–638PubMed
63.
Gaillard RC. Cytokines in the neuroendocrine system. Int Rev Immunol 1998; 17(1–4): 181–216PubMed
64.
Gaillard R. Interaction between the hypothalamo-pituitary-adrenal axis and the immunological system. Ann Endocrinol (Paris) 2001; 62(2): 155–63
65.
Maier SF, Watkins LR. Cytokines for psychologists: implications for bidirectional immune-to-brain communication for understanding behavior, mood, and cognition. Psychol Rev 1998; 105(1): 83–107PubMed
66.
Janeway CA, Travers P, Walport M, et al. Immunobiology: the immune system in health and disease. New York: Garland Publishing, 2001
67.
Berger A. Science commentary: Th1 and Th2 responses: what are they? BMJ 2000; 321: 424PubMed
68.
Ploegh HL. Viral strategies of immune evasion. Science 1998 Apr 10; 280: 248–53PubMed
69.
Morel AP, Oriss TB. Crossregulation between Th1 and Th2 cells. Crit Rev Immunol 1998; 18: 275–303PubMed
70.
Mosmann TR, Cherwinsk H, Bond MW, et al. Two types of murine helper T-cell clone: I. definition according to profiles of lymphokines activities and secreted proteins. J Immunol 1986; 136: 2348–57PubMed
71.
Romagnani S. T-cell subsets (Th1 versus Th2). Ann Allergy Asthma Immunol 2000; 85(1): 9–18PubMed
72.
Elenkov IJ, Chrousos GP, Wilder RL. Neuroendocrine regulation of IL-12 and TNF-alpha/IL-10 balance: clinical implications. Ann N Y Acad Sci 2000; 917: 94–105PubMed
73.
Romagnani S. Human TH1 and TH2 subsets: regulation of differentiation and role in protection and immunopathology. Int Arch Allergy Immunol 1996; 98(4): 279–85
74.
Romagnani S. Development of Th1- or Th2-dominated immune responses: what about the polarizing signals? Int J Clin Lab Res 1996; 26(2): 83–98PubMed
75.
Annunziato F, Galli G, Romagnani P, et al. Molecules associated with human Th1 or Th2 cells. Eur Cytokine Netw 1998;9(3 Suppl.): 12–6PubMed
76.
Romagnani S. Biology of human TH1 and TH2 cells. J Clin Immunol 1995; 15(3): 121–9PubMed
77.
Foster C. Monitoring training in athletes with reference to overtraining syndrome. Med Sci Sports Exerc 1998; 30(7): 1164–8PubMed
78.
Nieman DC, Johanssen LM, Lee JW. Infectious episodes in runners before and after a road race. J Sports Med Phys Fit 1989; 29: 289–96
79.
Nieman DC, Henson DA, Smith L, et al. Cytokine changes after a marathon race. J Appl Physiol 2001; 91: 109–14PubMed
80.
Shute M, Nieman DC, Smith L, et al. Influence of carbohydrate on the cytokine response to marathon running [abstract]. Med Sci Sports Exerc1999; 31(5): S60
81.
Dill DB, Costill DL. Calculation of percentage changes in volumes of blood, plasma, and red cells in dehydration. J Appl Physiol 1974; 37: 274–48
82.
Gannon GA, Rhind SG, Suzui M, et al. Circulating levels of peripheral blood leukocytes and cytokines following competitive cycling. Can J Appl Physiol 1997; 22: 133–47PubMed
83.
Sprenger H, Jacobs C, Nain M, et al. Enhanced release of cytokines, interleukin-2 receptors, and neopterin after longdistance running. Clin Immunol Immunopathol 1992; 63(2): 188–95PubMed
84.
Muns G, Rubenstein I, Singer P. Neutrophil chemotactic activity is increased in nasal secretions of long-distance runners. Int J Sports Med 1996; 17: 56–9PubMed
85.
Haahr PM, Pedersen BK, Fomsgaard A, et al. Effect of physical exercise on in vitro production of interleukin-1, interleukin-6, tumor necrosis factor-alpha, interleukin-2 and interferon-gamma. Int J Sports Med 1991; 12: 223–7PubMed
86.
Northoff H, Berg A. Immunologic mediators as parameters of the reaction to strenuous exercise. Int J Sports Med 1991; 12Suppl. 1: S9–15PubMed
87.
Steensberg A, Dyhr Toft A, Bruunsgaard H, et al. Strenuous exercise decreases the percentage of type 1 T cells in the circulation. J Appl Physiol 2001; 91: 1708–12PubMed
88.
Moldoveanu AI, Shepherd RJ, Shek PN. The cytokine response to physical activity and training. Sports Med 2001; 31(2): 115–44PubMed
89.
Akimoto T, Akama T, Tatsuno M, et al. Effect of brief maximal exercise on circulating levels of interleukin-12. Eur J Appl Physiol 2000; 81: 510–2PubMed
90.
Janeway CA, Traveers P, Walport M, et al. Immunobiology: the immune system in health and disease. London: Current Biology Publications, 1999
91.
Mercer J, Hogen E, Rananto C, et al. Eccentrically induced muscle damage and acute phase proteins [abstract]. Med Sci Sports Exerc 1999; 31(5): S61
92.
Nieman DC, Henson DA, Gusewitch G. Physical activity and immune function in elderly women. Med Sci Sports Exerc 1993; 25: 823–31PubMed
93.
Karalis K, Sano H, Redwine J, et al. Autocrine or paracrine inflammatory actions of corticotropin-releasing hormone in vivo. Science 1991; 254: 421–3PubMed
94.
Webster EL, Torpy DJ, Elenkov IJ, et al. Corticotropin-releaseing hormone and inflammation. Ann N Y Acad Sci 1998; 840: 21–32PubMed
95.
Chrousos GP, Torpy DJ, Gold PW. Interactions between the hypothalamic-pituitary-adrenal axis and the female reproductive system: clinical implications. Ann Intern Med 1998; 129(3): 229–40PubMed
96.
Schobitz B, Reul JMHM, Holsboer F. The role of the hypotha-lamic-pituitary-adrenocorticol system during inflammatory conditions. Crit Rev Neurobiol 1994; 8(4): 263–91PubMed
97.
Watkins AD. Hierarchical cortical control of neuroimmu-nomodulatory pathways. Neuropathol Appl Neurobiol 1994; 20: 423–31PubMed
98.
Lehmann M, Foster C, Dickhuth HH, et al. Autonomic imbalance hypothesis and overtraining syndrome. Med Sci Sports Exerc 1998; 30(7): 1140–5PubMed
99.
Suzuki K, Totsuka M, Nakaji S, et al. Endurance exercise causes interaction among stress hormones, cytokines, neutrophil dynamics, and muscle damage. J Appl Physiol 1999; 87(4): 1360–7PubMed
100.
Tvede N, Kappel M, Karlund K, et al. Evidence that the effect of bicyle exercise on blood mononuclear cell proliferative responses and subsets is mediated by epinephrine. Int J Sports Med1994; 15: 100–4PubMed
101.
Chrousos G. Stress, chronic inflammation, and emotional and physical well-being: concurrent effects and chronic sequelae. J Allergy Clin Immunol 2000; 106 (5 Suppl.): S275–91PubMed
102.
Woods JA. Exercise and neuroendocrine modulation of macrophage function. Int J Sports Med 2000; 21Suppl. 1: S24–30PubMed
103.
Ceddia MA, Woods JA. Exercise suppresses macrophage antigen presentation. J Appl Physiol 1999; 87(6): 2253–8PubMed
104.
Jonsdottir IH. Exercise immunology: neuroendocrine regulation of NK-cells. Int J Sports Med 2000; 21Suppl. 1: S20–3PubMed
105.
Rhind SG, Gannon GA, Suzui M, et al. Indomethacin inhibits circulating PGE2 and reverses postexercise suppression of natural killer cell activity. Am J Physiol 1999; 276 (5 Pt 2): R1496–505PubMed
106.
Kunkel SL, Chensue SW. Prostaglandins and the regulation of immune responses. In: Otterness I, Capetola R, Wong S, editors. Advances in inflammation research. Vol. 7. New York: Raven Press, 1984: 93–109
107.
Everts B, Wahrborg P, Hedner T. COX-2 specific inhibotors: the emergence of a new class of analgesic and anti-inflammatory drugs. Clin Rheum2000; 19(5): 331–43
108.
Ayala A, Lehmann DL, Herdon CD, et al. Mechansims of enhanced susceptibility to sepsis following hemorrhage: interleukine-10 suppression of T-cell response is mediated by eicosanoid-induced interleukin-4 disease. Arch Surg 1994; 129: 1172–8PubMed
109.
Smith LL, Wells JM, Houmard JA, et al. Increases in prostaglandin E2 after eccentric exercise: a preliminary report. Horm Metab Res 1993; 25: 451–2PubMed
110.
Pedersen BK, Tvede N, Klarlund K, et al. Indomethacin in vitro and in vivo abolishes postexercise suppression of natrual killer cell activity in peripheral blood. Int J Sports Med 1990; 11(2): 127–31PubMed
111.
Faist E, Markewitz A, Fuchs D, et al. Immunomodulatory therapy with thymopentin and indomethacin. Ann Surg 1991; 215: 264–75
Metadata
Title
Overtraining, Excessive Exercise, and Altered Immunity
Is This a T Helper-1 Versus T Helper-2 Lymphocyte Response?
Author
Lucille Lakier Smith
Publication date
01-04-2003
Publisher
Springer International Publishing
Published in
Sports Medicine / Issue 5/2003
Print ISSN: 0112-1642
Electronic ISSN: 1179-2035
DOI
https://doi.org/10.2165/00007256-200333050-00002