Skip to main content

Advertisement

SpringerLink
Log in

Exercising in Environmental Extremes

A Greater Threat to Immune Function?

  • Review Article
  • Published:
Sports Medicine Aims and scope Submit manuscript

Abstract

Athletes, military personnel, fire fighters, mountaineers and astronauts may be required to perform in environmental extremes (e.g. heat, cold, high altitude and microgravity). Exercising in hot versus thermoneutral conditions (where core temperature is ≥1°C higher in hot conditions) augments circulating stress hormones, catecholamines and cytokines with associated increases in circulating leukocytes. Studies that have clamped the rise in core temperature during exercise (by exercising in cool water) demonstrate a large contribution of the rise in core temperature in the leukocytosis and cytokinaemia of exercise. However, with the exception of lowered stimulated lymphocyte responses after exercise in the heat, and in exertional heat illness patients (core temperature >40°C), recent laboratory studies show a limited effect of exercise in the heat on neutrophil function, monocyte function, natural killer cell activity and mucosal immunity. Therefore, most of the available evidence does not support the contention that exercising in the heat poses a greater threat to immune function (vs thermoneutral conditions).

From a critical standpoint, due to ethical committee restrictions, most laboratory studies have evoked modest core temperature responses (<39°C). Given that core temperature during exercise in the field often exceeds levels associated with fever and hyperthermia (>39.5°C) field studies may provide an opportunity to determine the effects of severe heat stress on immunity. Field studies may also provide insight into the possible involvement of immune modulation in the aetiology of exertional heat stroke (core temperature >40.6°C) and identify the effects of acclimatisation on neuroendocrine and immune responses to exercise-heat stress. Laboratory studies can provide useful information by, for example, applying the thermal clamp model to examine the involvement of the rise in core temperature in the functional immune modifications associated with prolonged exercise.

Studies investigating the effects of cold, high altitude and microgravity on immunity and infection incidence are often hindered by extraneous stressors (e.g. isolation). Nevertheless, the available evidence does not support the popular belief that short- or long-term cold exposure, with or without exercise, suppresses immunity and increases infection incidence. In fact, controlled laboratory studies indicate immuno-stimulatory effects of cold exposure.

Although some evidence shows that ascent to high altitude increases infection incidence, clear conclusions are difficult to make because of some overlap with the symptoms of acute mountain sickness. Studies have reported suppressed cell-mediated immunity in mountaineers at high altitude and in astronauts after re-entering the normal gravity environment; however, the impact of this finding on resistance to infection remains unclear.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Table I
Fig. 2
Table II
Fig. 3
Table III
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Brenner IK, Shek PN, Shephard RJ. Infection in athletes. Sports Med 1994; 17: 86–107

    Article  PubMed  CAS  Google Scholar 

  2. Nieman DC, Johanssen LM, Lee JW, et al. Infectious episodes in runners before and after the Los Angeles Marathon. J Sports Med Phys Fitness 1990; 30: 316–28

    PubMed  CAS  Google Scholar 

  3. Peters EM, Bateman ED. Ultramarathon running and upper respiratory tract infections: an epidemiological survey. S Afr Med J 1983; 64: 582–4

    PubMed  CAS  Google Scholar 

  4. Kappel M, Tvede N, Galbo H, et al. Evidence that the effect of physical exercise on NK cell activity is mediated by epinephrine. J Appl Physiol 1991; 70: 2530–4

    PubMed  CAS  Google Scholar 

  5. Keast D, Cameron K, Morton AR. Exercise and the immune response. Sports Med 1988; 5: 248–67

    Article  PubMed  CAS  Google Scholar 

  6. Lewicki R, Tchorzewski H, Majewska E, et al. Effect of maximal physical exercise on T-lymphocyte subpopulations and on interleukin 1 (IL 1) and interleukin 2 (IL 2) production in vitro. Int J Sports Med 1988; 9: 114–7

    Article  PubMed  CAS  Google Scholar 

  7. Oshida Y, Yamanouchi K, Hayamizu S, et al. Effect of acute physical exercise on lymphocyte subpopulations in trained and untrained subjects. Int J Sports Med 1988; 9: 137–40

    Article  PubMed  CAS  Google Scholar 

  8. Robson PJ, Blannin AK, Walsh NP, et al. Effects of exercise intensity, duration and recovery on in vitro neutrophil function in male athletes. Int J Sports Med 1999; 20: 128–35

    PubMed  CAS  Google Scholar 

  9. Tomasi TB, Trudeau FB, Czerwinski D, et al. Immune parameters in athletes before and after strenuous exercise. J Clin Immunol 1982; 2: 173–8

    Article  PubMed  CAS  Google Scholar 

  10. Blannin AK, Robson PJ, Walsh NP, et al. The effect of exercising to exhaustion at different intensities on saliva immunoglobulin A, protein and electrolyte secretion. Int J Sports Med 1998; 19: 547–52

    Article  PubMed  CAS  Google Scholar 

  11. Nieman DC, Miller AR, Henson DA, et al. Effects of high- vs moderate-intensity exercise on natural killer cell activity. Med Sci Sports Exerc 1993; 25: 1126–34

    PubMed  CAS  Google Scholar 

  12. Bishop NC, Blannin AK, Walsh NP, et al. Nutritional aspects of immunosuppression in athletes. Sports Med 1999; 28: 151–76

    Article  PubMed  CAS  Google Scholar 

  13. Nieman DC. Exercise immunology: nutritional countermeasures. Can J Appl Physiol 2001; 26: S45–55

    Article  PubMed  CAS  Google Scholar 

  14. Clow A, Hucklebridge F. The impact of psychological stress on immune function in the athletic population. Exerc Immunol Rev 2001; 7: 5–17

    PubMed  CAS  Google Scholar 

  15. Hoffman-Goetz L, Pedersen BK. Exercise and the immune system: a model of the stress response? Immunol Today 1994; 15: 382–7

    Article  PubMed  CAS  Google Scholar 

  16. Shephard RJ. Immune changes induced by exercise in an adverse environment. Can J Physiol Pharmacol 1998; 76: 539–46

    Article  PubMed  CAS  Google Scholar 

  17. Jonsdottir IH. Special feature for the Olympics: effects of exercise on the immune system: neuropeptides and their interaction with exercise and immune function. Immunol Cell Biol 2000; 78: 562–70

    Article  PubMed  CAS  Google Scholar 

  18. Brenner I, Shek PN, Zamecnik J, et al. Stress hormones and the immunological responses to heat and exercise. Int J Sports Med 1998; 19: 130–43

    Article  PubMed  CAS  Google Scholar 

  19. Vale W, Spiess J, Rivier C, et al. Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin. Science 1981; 213: 1394–7

    Article  PubMed  CAS  Google Scholar 

  20. Tsigos C, Chrousos GP. Physiology of the hypothalamic-pituitary-adrenal axis in health and dysregulation in psychiatric and autoimmune disorders. Endocrinol Metab Clin North Am 1994; 23: 451–66

    PubMed  CAS  Google Scholar 

  21. Kappel M, Poulsen TD, Hansen MB, et al. Somatostatin attenuates the hyperthermia induced increase in neutrophil concentration. Eur J Appl Physiol 1998; 77: 149–56

    Article  CAS  Google Scholar 

  22. Woods J, Lu Q, Ceddia MA, et al. Special feature for the Olympics: effects of exercise on the immune system-exercise-induced modulation of macrophage function. Immunol Cell Biol 2000; 78: 545–53

    Article  PubMed  CAS  Google Scholar 

  23. Madden KS, Felten DL. Experimental basis for neuralimmune interactions. Physiol Rev 1995; 75: 77–106

    PubMed  CAS  Google Scholar 

  24. McCarthy DA, Dale MM. The leucocytosis of exercise: a re-view and model. Sports Med 1988; 6: 333–63

    Article  PubMed  CAS  Google Scholar 

  25. Tonnesen E, Christensen NJ, Brinklov MM. Natural killer cell activity during cortisol and adrenaline infusion in healthy volunteers. Eur J Clin Invest 1987; 17: 497–503

    Article  PubMed  CAS  Google Scholar 

  26. Elenkov IJ, Chrousos GP. Stress hormones, Th1/Th2 patterns, pro/anti-inflammatory cytokines and susceptibility to disease. Trends Endocrinol Metab 1999; 10: 359–68

    Article  PubMed  CAS  Google Scholar 

  27. Breuninger LM, Dempsey WL, Uhl J, et al. Hydrocortisone regulation of interleukin-6 protein production by a purified population of human peripheral blood monocytes. Clin Immunol Immunopathol 1993; 69: 205–14

    Article  PubMed  CAS  Google Scholar 

  28. Chrousos GP. The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation. N Engl J Med 1995; 332: 1351–62

    Article  PubMed  CAS  Google Scholar 

  29. Elenkov IJ, Papanicolaou DA, Wilder RL, et al. Modulatory effects of glucocorticoids and catecholamines on human interleukin-12 and interleukin-10 production: clinical implications. Proc Assoc Am Physicians 1996; 108: 374–81

    PubMed  CAS  Google Scholar 

  30. Waage A, Slupphaug G, Shalaby R. Glucocorticoids inhibit the production of IL6 from monocytes, endothelial cells and fibroblasts. Eur J Immunol 1990; 20: 2439–43

    Article  PubMed  CAS  Google Scholar 

  31. Wu CY, Wang K, McDyer JF, et al. Prostaglandin E2 and dexamethasone inhibit IL-12 receptor expression and IL-12 responsiveness. J Immunol 1998; 161: 2723–30

    PubMed  CAS  Google Scholar 

  32. Morel PA, Oriss TB. Crossregulation between Th1 and Th2 cells. Crit Rev Immunol 1998; 18: 275–303

    Article  PubMed  CAS  Google Scholar 

  33. Ramierz F, Fowell DJ, Puklavec M, et al. Glucocorticoids promote a TH2 cytokine response by CD4+ T cells in vitro. J Immunol 1996; 156: 2406–12

    Google Scholar 

  34. Lindquist S. The heat-shock response. Annu Rev Biochem 1986; 55: 1151–91

    Article  PubMed  CAS  Google Scholar 

  35. Ding XZ, Fernandez-Prada CM, Bhattacharjee AK, et al. Over-expression of hsp-70 inhibits bacterial lipopolysaccharide-induced production of cytokines in human monocyte-derived macrophages. Cytokine 2001; 16: 210–9

    Article  PubMed  CAS  Google Scholar 

  36. Sun D, Chen D, Du B, et al. Heat shock response inhibits NF-kappaB activation and cytokine production in murine Kupffer cells. J Surg Res 2005; 129: 114–21

    Article  PubMed  CAS  Google Scholar 

  37. Moseley PL. Exercise, stress, and the immune conversation. Exerc Sport Sci Rev 2000; 28: 128–32

    PubMed  CAS  Google Scholar 

  38. Asea A. Chaperokine-induced signal transduction pathways. Exerc Immunol Rev 2003; 9: 25–33

    PubMed  Google Scholar 

  39. Vabulas RM, Ahmad-Nejad P, Ghose S, et al. HSP70 as endogenous stimulus of the toll/interleukin-1 receptor signal pathway. J Biol Chem 2002; 277: 15107–12

    Article  PubMed  CAS  Google Scholar 

  40. Febbraio MA, Ott P, Nielsen HB, et al. Exercise induces hepatosplanchnic release of heat shock protein 72 in humans. J Physiol 2002; 544: 957–62

    Article  PubMed  CAS  Google Scholar 

  41. Fehrenbach E, Niess AM. Role of heat shock proteins in the exercise response. Exerc Immunol Rev 1999; 5: 57–77

    PubMed  CAS  Google Scholar 

  42. Lancaster GI, Moller K, Nielsen B, et al. Exercise induces the release of heat shock protein 72 from the human brain in vivo. Cell Stress Chaperones 2004; 9: 276–80

    Article  PubMed  CAS  Google Scholar 

  43. Walsh RC, Koukoulas I, Garnham A, et al. Exercise increases serum Hsp72 in humans. Cell Stress Chaperones 2001; 6: 386–93

    Article  PubMed  CAS  Google Scholar 

  44. Fleshner M, Campisi J, Johnson JD. Can exercise stress facilitate innate immunity? A functional role for stress-induced extracellular Hsp72. Exerc Immunol Rev 2003; 9: 6–24

    Google Scholar 

  45. Fleshner M, Johnson JD. Endogenous extra-cellular heat shock protein 72: releasing signal(s) and function. Int J Hyperthermia 2005; 21: 457–71

    Article  PubMed  CAS  Google Scholar 

  46. Niess AM, Dickhuth HH, Northoff H, et al. Free radicals and oxidative stress in exercise: immunological aspects. Exerc Immunol Rev 1999; 5: 22–56

    PubMed  CAS  Google Scholar 

  47. Bennett IL, Nicastri A. Fever as a mechanism of resistance. Bacteriol Rev 1960; 24: 16–34

    PubMed  Google Scholar 

  48. Hanson DF. Fever, temperature, and the immune response. Ann N Y Acad Sci 1997; 813: 453–64

    Article  PubMed  CAS  Google Scholar 

  49. Kluger MJ, Ringler DH, Anver MR. Fever and survival. Science 1975; 188: 166–8

    Article  PubMed  CAS  Google Scholar 

  50. Callahan TE, Marins J, Welch WJ, et al. Heat shock attenuates oxidation and accelerates apoptosis in human neutrophils. J Surg Res 1999; 85: 317–22

    Article  PubMed  CAS  Google Scholar 

  51. Fildes J, Fisher S, Sheaff CM, et al. Effects of short heat exposure on human red and white blood cells. J Trauma 1998; 45: 479–84

    Article  PubMed  CAS  Google Scholar 

  52. Frohlich D, Wittmann S, Rothe G, et al. Mild hyperthermia down-regulates receptor-dependent neutrophil function. Anesth Analg 2004; 99: 284–92

    Article  PubMed  Google Scholar 

  53. Roberts NJ, Steigbigel RT. Hyperthermia and human leukocyte functions: effects on response of lymphocytes to mitogen and antigen and bactericidal capacity of monocytes and neutrophils. Infect Immun 1977; 18: 673–9

    PubMed  Google Scholar 

  54. Grogan JB, Parks LC, Minaberry D. Polymorphonuclear leukocyte function in cancer patients treated with total body hyperthermia. Cancer 1980; 45: 2611–5

    Article  PubMed  CAS  Google Scholar 

  55. Nakayama J, Nakao T, Mashino T, et al. Kinetics of immunological parameters in patients with malignant melanoma treated with hyperthermic isolated limb perfusion. J Dermatol Sci 1997; 15: 1–8

    Article  PubMed  CAS  Google Scholar 

  56. Park MM, Hornback NB, Endres S, et al. The effect of whole body hyperthermia on the immune cell activity of cancer patients. Lymphokine Res 1990; 9: 213–23

    PubMed  CAS  Google Scholar 

  57. Katschinski DM, Wiedemann GJ, Longo W, et al. Whole body hyperthermia cytokine induction: a review, and unifying hypothesis for myeloprotection in the setting of cytotoxic therapy. Cytokine Growth Factor Rev 1999; 10: 93–7

    Article  PubMed  CAS  Google Scholar 

  58. Robins HI, Cohen JD, Schmitt CL, et al. Phase I clinical trial of carboplatin and 41.8 degrees C whole-body hyperthermia in cancer patients. J Clin Oncol 1993; 11: 1787–94

    PubMed  CAS  Google Scholar 

  59. Robins HI, Longo WL, Lagoni RK, et al. Phase I trial of lonidamine with whole body hyperthermia in advanced cancer. Cancer Res 1988; 48: 6587–92

    PubMed  CAS  Google Scholar 

  60. Robins HI, Dennis WH, Steeves RA, et al. A proposal for the Robins HI, Dennis WH, Steeves RA, et al. A proposal for the chronic leukemia. J Clin Oncol 1984; 2: 1050–6

    CAS  Google Scholar 

  61. Ernst E. Sauna: a hobby or for health? J R Soc Med 1989; 82: 639

    PubMed  CAS  Google Scholar 

  62. Ernst E, Pecho E, Wirz P, et al. Regular sauna bathing and the incidence of common colds. Ann Med 1990; 22: 225–7

    Article  PubMed  CAS  Google Scholar 

  63. Cross MC, Radomski MW, VanHelder WP, et al. Endurance exercise with and without a thermal clamp: effects on leukocytes and leukocyte subsets. J Appl Physiol 1996; 81: 822–9

    PubMed  CAS  Google Scholar 

  64. Rhind SG, Gannon GA, Shek PN, et al. Contribution of exertional hyperthermia to sympathoadrenal-mediated lymphocyte subset redistribution. J Appl Physiol 1999; 87: 1178–85

    PubMed  CAS  Google Scholar 

  65. Rhind SG, Gannon GA, Shephard RJ, et al. Cytokine induction during exertional hyperthermia is abolished by core temperature clamping: neuroendocrine regulatory mechanisms. Int J Hyperthermia 2004; 20: 503–16

    Article  PubMed  CAS  Google Scholar 

  66. Pugh LG, Corbett JL, Johnson RH. Rectal temperatures, weight losses, and sweat rates in marathon running. J Appl Physiol 1967; 23: 347–52

    PubMed  CAS  Google Scholar 

  67. Roberts WO. Exercise-associated collapse in endurance events: a classification system. Physician Sportsmed 1989; 17: 49–55

    Google Scholar 

  68. Shephard RJ, Shek PN. Immune dysfunction as a factor in heat illness. Crit Rev Immunol 1999; 19: 285–302

    PubMed  CAS  Google Scholar 

  69. Lim CL, Mackinnon LT. The roles of exercise-induced immune system disturbances in the pathology of heat stroke: the dual pathway model of heat stroke. Sports Med 2006; 36: 39–64

    Article  PubMed  Google Scholar 

  70. Cohen P, Warren SL. A study of the leukocytosis produced in man by artificial fever. J Clin Invest 1935; 14: 423–33

    Article  PubMed  CAS  Google Scholar 

  71. Downing JF, Taylor MW. The effect of in vivo hyperthermia on selected lymphokines in man. Lymphokine Res 1987; 6: 103–9

    PubMed  CAS  Google Scholar 

  72. Downing JF, Martinez-Valdez H, Elizondo RS, et al. Hyperthermia in humans enhances interferon-gamma synthesis and alters the peripheral lymphocyte population. J Interferon Res 1988; 8: 143–50

    Article  PubMed  CAS  Google Scholar 

  73. Severs Y, Brenner I, Shek PN, et al. Effects of heat and intermittent exercise on leukocyte and sub-population cell counts. Eur J Appl Physiol 1996; 74: 234–45

    Article  CAS  Google Scholar 

  74. Kappel M, Stadeager C, Tvede N, et al. Effects of in vivo hyperthermia on natural killer cell activity, in vitro proliferative responses and blood mononuclear cell subpopulations. Clin Exp Immunol 1991; 84: 175–80

    Article  PubMed  CAS  Google Scholar 

  75. Zanker KS, Lange J. Whole body hyperthermia and natural killer cell activity. Lancet 1982; I: 1079–80

    Article  Google Scholar 

  76. Dahn MS, Whitcomb MP, Lange MP, et al. Altered T-lymphocyte subsets in severe sepsis. Am Surg 1988; 54: 450–5

    PubMed  CAS  Google Scholar 

  77. Mackinnon LT. Advances in exercise immunology. Champaign (IL): Human Kinetics, 1999

    Google Scholar 

  78. Bouchama A, al Hussein K, Adra C, et al. Distribution of peripheral blood leukocytes in acute heatstroke. J Appl Physiol 1992; 73: 405–9

    PubMed  CAS  Google Scholar 

  79. Ellis GS, Carlson DE, Hester L, et al. G-CSF, but not corticosterone, mediates circulating neutrophilia induced by febrilerange hyperthermia. J Appl Physiol 2005; 98: 1799–804

    Article  PubMed  CAS  Google Scholar 

  80. Ryan AJ, Flanagan SW, Moseley PL, et al. Acute heat stress protects rats against endotoxin shock. J Appl Physiol 1992; 73: 1517–22

    PubMed  CAS  Google Scholar 

  81. DuBose DA, McCreary J, Sowders L, et al. Relationship between rat heat stress mortality and alterations in reticuloendothelial carbon clearance function. Aviat Space Environ Med 1983; 54: 1090–5

    Google Scholar 

  82. Jiang Q, Cross AS, Singh IS, et al. Febrile core temperature is essential for optimal host defense in bacterial peritonitis. Infect Immun 2000; 68: 1265–70

    Article  PubMed  CAS  Google Scholar 

  83. Marino MW, Dunn A, Grail D, et al. Characterization of tumor necrosis factor-deficient mice. Proc Natl Acad Sci U S A 1997; 94: 8093–8

    Article  PubMed  CAS  Google Scholar 

  84. Bouchama A, Knochel JP. Heat stroke. N Engl J Med 2002; 346: 1978–88

    Article  PubMed  CAS  Google Scholar 

  85. Hasday JD, Singh IS. Fever and the heat shock response: distinct, partially overlapping processes. Cell Stress Chaperones 2000; 5: 471–80

    Article  PubMed  CAS  Google Scholar 

  86. D’Oleire F, Schmitt CL, Robins HI, et al. Cytokine induction in humans by 41.8 degrees C whole-body hyperthermia. J Natl Cancer Inst 1993; 85: 833–4

    Article  PubMed  Google Scholar 

  87. Robins HI, Kutz M, Wiedemann GJ, et al. Cytokine induction by 41.8 degrees C whole body hyperthermia. Cancer Lett 1995; 97: 195–201

    Article  PubMed  CAS  Google Scholar 

  88. Demetri GD, Griffin JD. Granulocyte colony-stimulating factor and its receptor. Blood 1991; 78: 2791–808

    PubMed  CAS  Google Scholar 

  89. Robins HI, Rushing D, Kutz M, et al. Phase I clinical trial of melphalan and 41.8 degrees C whole-body hyperthermia in cancer patients. J Clin Oncol 1997; 15: 158–64

    PubMed  CAS  Google Scholar 

  90. Nahas GG, Tannieres ML, Lennon JF. Direct measurement of leukocyte motility: effects of pH and temperature. Proc Soc Exp Biol Med 1971; 138: 350–2

    PubMed  CAS  Google Scholar 

  91. Kappel M, Kharazmi A, Nielsen H, et al. Modulation of the counts and functions of neutrophils and monocytes under in vivo hyperthermia conditions. Int J Hyperthermia 1994; 10: 165–73

    Article  PubMed  CAS  Google Scholar 

  92. Bozzetti F, Cozzaglio L, Villa ML, et al. Restorative effect of total parenteral nutrition on natural killer cell activity in malnourished cancer patients. Eur J Cancer 1995; 31A: 2023–7

    Article  PubMed  CAS  Google Scholar 

  93. Puente J, Carvajal T, Parra S, et al. In vitro studies of natural killer cell activity in septic shock patients: response to a challenge with alpha-interferon and interleukin-2. Int J Clin Pharmacol Ther Toxicol 1993; 31: 271–5

    PubMed  CAS  Google Scholar 

  94. Simms HH, Gaither TA, Fries LF, et al. Monokines released during short-term Fc gamma receptor phagocytosis up-regulate polymorphonuclear leukocytes and monocyte-phagocytic function. J Immunol 1991; 147: 265–72

    PubMed  CAS  Google Scholar 

  95. Onozaki K, Matsushima K, Kleinerman ES, et al. Role of interleukin 1 in promoting human monocyte-mediated tumor cytotoxicity. J Immunol 1985; 135: 314–20

    PubMed  CAS  Google Scholar 

  96. Philip R. Cytolysis of tumor necrosis factor (TNF)-resistant tumor targets: differential cytotoxicity of monocytes activated by the interferons, IL-2, and TNF. J Immunol 1988; 140: 1345–9

    PubMed  CAS  Google Scholar 

  97. Northoff H, Berg A, Weinstock C. Similarities and differences of the immune response to exercise and trauma: the IFN-gamma concept. Can J Physiol Pharmacol 1998; 76: 497–504

    Article  PubMed  CAS  Google Scholar 

  98. Ghussen F, Kruger I, Groth W, et al. The role of regional hyperthermic cytostatic perfusion in the treatment of extremity melanoma. Cancer 1988; 61: 654–9

    Article  PubMed  CAS  Google Scholar 

  99. Skene AI, Bulman AS, Williams TR, et al. Hyperthermic isolated perfusion with melphalan in the treatment of advanced malignant melanoma of the lower limb. Br J Surg 1990; 77: 765–7

    Article  PubMed  CAS  Google Scholar 

  100. De Maeyer E, Maeyer-Guignard J. Immuno-modulating properties of interferons. Philos Trans R Soc Lond B Biol Sci 1982; 299: 77–90

    Article  PubMed  Google Scholar 

  101. Hanson DF, Murphy PA, Silicano R, et al. The effect of temperature on the activation of thymocytes by interleukins I and II. J Immunol 1983; 130: 216–21

    PubMed  CAS  Google Scholar 

  102. Fairchild KD, Viscardi RM, Hester L, et al. Effects of hypothermia and hyperthermia on cytokine production by cultured human mononuclear phagocytes from adults and newborns. J Interferon Cytokine Res 2000; 20: 1049–55

    Article  PubMed  CAS  Google Scholar 

  103. Febbraio MA. Alterations in energy metabolism during exercise and heat stress. Sports Med 2001; 31: 47–59

    Article  PubMed  CAS  Google Scholar 

  104. Galbo H, Houston ME, Christensen NJ, et al. The effect of water temperature on the hormonal response to prolonged swimming. Acta Physiol Scand 1979; 105: 326–37

    Article  PubMed  CAS  Google Scholar 

  105. Galloway SD, Maughan RJ. Effects of ambient temperature on the capacity to perform prolonged cycle exercise in man. Med Sci Sports Exerc 1997; 29: 1240–9

    Article  PubMed  CAS  Google Scholar 

  106. Malm C. Exercise immunology: the current state of man and mouse. Sports Med 2004; 34: 555–66

    Article  PubMed  Google Scholar 

  107. Nieman DC. Current perspective on exercise immunology. Curr Sports Med Rep 2003; 2: 239–42

    PubMed  Google Scholar 

  108. Mitchell JB, Dugas JP, McFarlin BK, et al. Effect of exercise, heat stress, and hydration on immune cell number and func-tion. Med Sci Sports Exerc 2002; 34: 1941–50

    Article  PubMed  CAS  Google Scholar 

  109. Niess AM, Fehrenbach E, Lehmann R, et al. Impact of elevated ambient temperatures on the acute immune response to intensive endurance exercise. Eur J Appl Physiol 2003; 89: 344–51

    Article  PubMed  CAS  Google Scholar 

  110. Laing S, Blackwell J, Gwynne D, et al. Neutrophil degranulation response to 2h of exercise in a 30°C environment. Aviat Space Environ Med 2005; 76: 1068–73

    PubMed  Google Scholar 

  111. McFarlin BK, Mitchell JB. Exercise in hot and cold environ-ments: differential effects on leukocyte number and NK cell activity. Aviat Space Environ Med 2003; 74: 1231–6

    PubMed  Google Scholar 

  112. Brenner IKM, Castellani JW, Gabaree C, et al. Immune changes in humans during cold exposure: effects of prior heating and exercise. J Appl Physiol 1999; 87: 699–710

    PubMed  CAS  Google Scholar 

  113. Pedersen BK, Bruunsgaard H, Klokker M, et al. Exercise-induced immunomodulation: possible roles of neuroendocrine and metabolic factors. Int J Sports Med 1997; 18 Suppl. 1: S2–7

    Article  PubMed  CAS  Google Scholar 

  114. Yamada M, Suzuki K, Kudo S, et al. Raised plasma G-CSF and IL-6 after exercise may play a role in neutrophil mobilization into the circulation. J Appl Physiol 2002; 92: 1789–94

    PubMed  CAS  Google Scholar 

  115. Neville AJ, Sauder DN. Whole body hyperthermia (41–42 degrees C) induces interleukin-1 in vivo. Lymphokine Res 1988; 7: 201–6

    PubMed  CAS  Google Scholar 

  116. Jiang Q, Detolla L, Singh IS, et al. Exposure to febrile temperature upregulates expression of pyrogenic cytokines in endotoxin-challenged mice. Am J Physiol 1999; 276: R1653–60

    PubMed  CAS  Google Scholar 

  117. Kappel M, Diamant M, Hansen MB, et al. Effects of in vitro hyperthermia on the proliferative response of blood mononuclear cell subsets, and detection of interleukins 1 and 6, tumour necrosis factor-alpha and interferon-gamma. Immunology 1991; 73: 304–8

    PubMed  CAS  Google Scholar 

  118. Pedersen BK. Special feature for the Olympics: effects of exercise on the immune system-exercise and cytokines. Immunol Cell Biol 2000; 78: 532–5

    Article  PubMed  CAS  Google Scholar 

  119. Cross A, Asher L, Seguin M, et al. The importance of a lipopolysaccharide-initiated, cytokine-mediated host defense ichia coli. J Clin Invest 1995; 96: 676–86

    Article  PubMed  CAS  Google Scholar 

  120. Cross AS, Sadoff JC, Kelly N, et al. Pretreatment with recombinant murine tumor necrosis factor alpha/cachectin and murine interleukin 1 alpha protects mice from lethal bacterial infection. J Exp Med 1989; 169: 2021–7

    Article  PubMed  CAS  Google Scholar 

  121. Starkie RL, Hargreaves M, Rolland J, et al. Heat stress, cytokines, and the immune response to exercise. Brain Behav Immun 2005; 19: 404–12

    Article  PubMed  CAS  Google Scholar 

  122. Montain SJ, Latzka WA, Sawka MN. Impact of muscle injury and accompanying inflammatory response on thermoregulation during exercise in the heat. J Appl Physiol 2000; 89: 1123–30

    PubMed  CAS  Google Scholar 

  123. Niess AM, Passek F, Lorenz I, et al. Expression of the antioxidant stress protein heme oxygenase-1 (HO-1) in human leukocytes. Free Rad Bio Med 1999; 26: 184–92

    Article  CAS  Google Scholar 

  124. Wilckens T, De Rijk R. Glucocorticoids and immune function: unknown dimensions and new frontiers. Immunol Today 1997; 18: 418–24

    Article  PubMed  CAS  Google Scholar 

  125. Laing SJ, Walsh NP, Walters R, et al. The effects of prolonged exercise in a hot environment on lipopolysaccharide (LPS)-stimulated monocyte TNF-a release in trained male cyclists. J Physiol 2003: 555P: PC88

    Google Scholar 

  126. Febbraio MA, Steensberg A, Keller C, et al. Glucose ingestion attenuates interleukin-6 release from contracting skeletal muscle in humans. J Physiol 2003; 549: 607–12

    Article  PubMed  CAS  Google Scholar 

  127. Hiscock N, Chan MH, Bisucci T, et al. Skeletal myocytes are a source of interleukin-6 mRNA expression and protein release during contraction: evidence of fiber type specificity. FASEB J 2004; 18: 992–4

    PubMed  CAS  Google Scholar 

  128. Steensberg A, Febbraio MA, Osada T, et al. Interleukin-6 production in contracting human skeletal muscle is influenced by 633–9 pre-exercise muscle glycogen content. J Physiol 2001; 537: 633–9

    Article  PubMed  CAS  Google Scholar 

  129. Starkie RL, Hargreaves M, Lambert DL, et al. Effect of temperature on muscle metabolism during submaximal exercise in humans. Exp Physiol 1999; 84: 775–84

    Article  PubMed  CAS  Google Scholar 

  130. Febbraio MA, Snow RJ, Hargreaves M, et al. Muscle metabolism during exercise and heat stress in trained men: effect of acclimation. J Appl Physiol 1994; 76: 589–97

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  132. Febbraio MA, Steensberg A, Starkie RL, et al. Skeletal muscle interleukin-6 and tumor necrosis factor-alpha release in healthy subjects and patients with type 2 diabetes at rest and during exercise. Metabolism 2003; 52: 939–44

    Article  PubMed  CAS  Google Scholar 

  133. Laing SJ, Gwynne D, Blackwell J, et al. Salivary IgA response to prolonged exercise in a hot environment in trained cyclists. Eur J Appl Physiol 2005; 93: 665–71

    Article  PubMed  CAS  Google Scholar 

  134. Muldoon S, Deuster P, Brandom B, et al. Is there a link between malignant hyperthermia and exertional heat illness? Exerc Sport Sci Rev 2004; 32: 174–9

    Article  PubMed  Google Scholar 

  135. Bouchama A, Parhar RS, el Yazigi A, et al. Endotoxemia and release of tumor necrosis factor and interleukin 1 alpha in acute heatstroke. J Appl Physiol 1991; 70: 2640–4

    PubMed  CAS  Google Scholar 

  136. Hammami MM, Bouchama A, al Sedairy S, et al. Concentrations of soluble tumor necrosis factor and interleukin-6 receptors in heatstroke and heator antagonist. Neurosci Res 1996; 24: 159–63tstress. Crit Care Med 1997; 25: 1314–9

    Article  Google Scholar 

  137. Moseley PL, Gapen C, Wallen ES, et al. Thermal stress induces epithelial permeability. Am J Physiol 1994; 267: C425–34

    PubMed  CAS  Google Scholar 

  138. Hall DM, Buettner GR, Matthes RD, et al. Hyperthermia stimulates nitric oxide formation: electron paramagnetic resonance detection of NO-heme in blood. J Appl Physiol 1994; 77: 548–53

    PubMed  CAS  Google Scholar 

  139. Lambert GP. Role of gastrointestinal permeability in exertional heatstroke. Exerc Sport Sci Rev 2004; 32: 185–90

    Article  PubMed  Google Scholar 

  140. Gathiram P, Wells MT, Brock-Utne JG, et al. Prevention of endotoxaemia by non-absorbable antibiotics in heat stress. J Clin Pathol 1987; 40: 1364–8

    Article  PubMed  CAS  Google Scholar 

  141. Chiu WT, Kao TY, Lin MT. Increased survival in experimental rat heatstroke by continuous perfusion of interleukin-1 receptor antagonist. Neurosci Res 1996; 24: 159–63

    Article  PubMed  CAS  Google Scholar 

  142. Baker B, Gaffin SL, Wells M, et al. Endotoxaemia in racehorses following exertion. J S Afr Vet Assoc 1988; 59: 63–6

    PubMed  CAS  Google Scholar 

  143. Bosenberg AT, Brock-Utne JG, Gaffin SL, et al. Strenuous exercise causes systemic endotoxemia. J Appl Physiol 1988; 65: 106–8

    PubMed  CAS  Google Scholar 

  144. Brock-Utne JG, Gaffin SL, Wells MT, et al. Endotoxaemia in exhausted runners after a long-distance race. S Afr Med J 1988; 73: 533–6

    PubMed  CAS  Google Scholar 

  145. Jeukendrup AE, Vet-Joop K, Sturk A, et al. Relationship between gastro-intestinal complaints and endotoxaemia, cytokine release and the acute-phase reaction during and after a long-distance triathlon in highly trained men. Clin Sci 2000; 98: 47–55

    Article  PubMed  CAS  Google Scholar 

  146. Marshall JC, Christou NV, Meakins JL. Immunomodulation by altered gastrointestinal tract flora: the effects of orally administered, killed Staphylococcus epidermidis, Candida, and Pseudomonas on systemic immune responses. Arch Surg 1988; 123: 1465–9

    Article  PubMed  CAS  Google Scholar 

  147. Ducreux S, Zorzato F, Muller C, et al. Effect of ryanodine receptor mutations on interleukin-6 release and intracellular calcium homeostasis in human myotubes from malignant hyperthermia-susceptible individuals and patients affected by central core disease. J Biol Chem 2004; 279: 43838–46

    Article  PubMed  CAS  Google Scholar 

  148. Hammami MM, Bouchama A, Shail E, et al. Lymphocyte subsets and adhesion molecules expression in heatstroke and heat stress. J Appl Physiol 1998; 84: 1615–21

    PubMed  CAS  Google Scholar 

  149. DuBose DA, Wenger CB, Flinn SD, et al. Distribution and mitogen response of peripheral blood lymphocytes following exertional heat injury. J Appl Physiol 2003; 95: 2381–9

    Google Scholar 

  150. Castellani JW, IK MB, Rhind SG. Cold exposure: human immune responses and intracellular cytokine expression. Med Sci Sports Exerc 2002; 34: 2013–20

    Article  PubMed  CAS  Google Scholar 

  151. Shephard RJ, Shek PN. Cold exposure and immune function. Can J Physiol Pharmacol 1998; 76: 828–36

    Article  PubMed  CAS  Google Scholar 

  152. Ritzel G. Critical evaluation of vitamin C as a prophylactic and therapeutic agent in colds. Helv Med Acta 1961; 28: 63–8

    PubMed  CAS  Google Scholar 

  153. Sabiston BH, Livingstone SD. Investigation of health problems related to Canadian northern military operations. Toronto: Defence and Civil Institute of Environmental Medicine, 1973

    Google Scholar 

  154. Armstrong LE. Performing in extreme environments. Champaign (IL): Human Kinetics, 2000

    Google Scholar 

  155. Jansky L, Pospisilova D, Honzova S, et al. Immune system of cold-exposed and cold-adapted humans. Eur J Appl Physiol 1996; 72: 445–50

    Article  CAS  Google Scholar 

  156. Wenisch C, Narzt E, Sessler DI, et al. Mild intraoperative hypothermia reduces production of reactive oxygen intermediates by polymorphonuclear leukocytes. Anesth Analg 1996; 82: 810–6

    PubMed  CAS  Google Scholar 

  157. Beilin B, Shavit Y, Razumovsky J, et al. Effects of mild perioperative hypothermia on cellular immune responses. Anesthesiology 1998; 89: 1133–40

    Article  PubMed  CAS  Google Scholar 

  158. Lackovic V, Borecky L, Vigas M, et al. Activation of NK cells in subjects exposed to mild hyper- or hypothermic load. J Interferon Res 1988; 8: 393–402

    Article  PubMed  CAS  Google Scholar 

  159. Doubt TJ. Physiology of exercise in the cold. Sports Med 1991; 11: 367–81

    Article  PubMed  CAS  Google Scholar 

  160. Timmons BA, Araujo J, Thomas TR. Fat utilization enhanced by exercise in a cold environment. Med Sci Sports Exerc 1985; 17: 673–8

    Article  PubMed  CAS  Google Scholar 

  161. Pitsiladis YP, Maughan RJ. The effects of exercise and diet manipulation on the capacity to perform prolonged exercise in the heat and in the cold in trained humans. J Physiol 1999; 517: 919–30

    Article  PubMed  CAS  Google Scholar 

  162. Housh TJ, Johnson GO, Housh DJ, et al. The effect of exercise at various temperatures on salivary levels of immunoglobulin A. Int J Sports Med 1991; 12: 498–500

    Article  PubMed  CAS  Google Scholar 

  163. Walsh NP, Blannin AK, Clark AM, et al. The effects of highintensity intermittent exercise on saliva IgA, total protein and alpha-amylase. J Sports Sci 1999; 17: 129–34

    Article  PubMed  CAS  Google Scholar 

  164. Walsh NP, Bishop NC, Blackwell J, et al. Salivary IgA response to prolonged exercise in a cold environment in trained cyclists. Med Sci Sports Exerc 2002; 34: 1632–7

    Article  PubMed  CAS  Google Scholar 

  165. Francis JL, Gleeson M, Lugg DJ, et al. Trends in mucosal immunity in Antarctica during six Australian winter expeditions. Immunol Cell Biol 2002; 80: 382–90

    Article  PubMed  CAS  Google Scholar 

  166. Gleeson M, Francis JL, Lugg DJ, et al. One year in Antarctica: mucosal immunity at three Australian stations. Immunol Cell Biol 2000; 78: 616–22

    Article  PubMed  CAS  Google Scholar 

  167. Bosch JA, Ring C, de Geus EJ, et al. Stress and secretory immunity. Int Rev Neurobiol 2002; 52: 213–53

    Article  PubMed  CAS  Google Scholar 

  168. Stone AA, Cox DS, Valdimarsdottir H, et al. Evidence that secretory IgA antibody is associated with daily mood. J Pers Soc Psychol 1987; 52: 988–93

    Article  PubMed  CAS  Google Scholar 

  169. Williams DL, Climie A, Muller HK, et al. Cell-mediated immunity in healthy adults in Antarctica and the sub-Antarctic. J Clin Lab Immunol 1986; 20: 43–9

    PubMed  CAS  Google Scholar 

  170. Muller HK, Lugg DJ, Quinn D. Cell mediated immunity in Antarctic wintering personnel; 1984–1992. Immunol Cell Biol 1995; 73: 316–20

    Article  PubMed  CAS  Google Scholar 

  171. Gard S. Respiratory virus infections other than influenza. Arch Environ Health 1968; 17: 543–6

    PubMed  CAS  Google Scholar 

  172. Shephard RJ, Castellani JW, Shek PN. Immune deficits induced by strenuous exertion under adverse environmental conditions: manifestations and countermeasures. Crit Rev Immunol 1998; 18: 545–68

    Article  PubMed  CAS  Google Scholar 

  173. Clothier JG. Medical aspects of work in Arctic areas. Practitioner 1974; 213: 805–11

    PubMed  CAS  Google Scholar 

  174. Edwards S, Hucklebridge F, Clow A, et al. Components of the diurnal cortisol cycle in relation to upper respiratory symptoms and perceived stress. Psych Med 2003; 65: 320–7

    Article  Google Scholar 

  175. Giesbrecht GG. The respiratory system in a cold environment. Aviat Space Environ Med 1995; 66: 890–902

    PubMed  CAS  Google Scholar 

  176. Halkier-Sorensen L, Menon GK, Elias PM, et al. Cutaneous barrier function after cold exposure in hairless mice: a model to demonstrate how cold interferes with barrier homeostasis among workers in the fish-processing industry. Br J Dermatol 1995; 132: 391–401

    Article  PubMed  CAS  Google Scholar 

  177. Bailey DM, Davies B, Castell LM, et al. Symptoms of infection and acute mountain sickness; associated metabolic sequelae and problems in differential diagnosis. High Alt Med Biol 2003; 4: 319–31

    Article  PubMed  CAS  Google Scholar 

  178. Singh I, Chohan IS, Lal M, et al. Effects of high altitude stay on the incidence of common diseases in man. Int J Biometeorol 1977; 21: 93–122

    Article  PubMed  CAS  Google Scholar 

  179. Basnyat B, Cumbo TA, Edelman R. Infections at high altitude. Clin Infect Dis 2001; 33: 1887–91

    Article  PubMed  CAS  Google Scholar 

  180. Meehan RT. Immune suppression at high altitude. Ann Emerg Med 1987; 16: 974–9

    Article  PubMed  CAS  Google Scholar 

  181. Ehrlich R, Mieszkuc BJ. Effects of space cabin environment on resistance to infection. I. Effect of 18,000-foot altitude on resistance to respiratory infection. J Infect Dis 1962; 110: 278–81

    CAS  Google Scholar 

  182. Highman B, Altland PD. A new method for the production of experimental bacterial endocarditis. Proc Soc Exp Biol Med 1950; 75: 573–7

    PubMed  CAS  Google Scholar 

  183. Meehan R, Duncan U, Neale L, et al. Operation Everest II: alterations in the immune system at high altitudes. J Clin Immunol 1988; 8: 397–406

    Article  PubMed  CAS  Google Scholar 

  184. Facco M, Zilli C, Siviero M, et al. Modulation of immune response by the acute and chronic exposure to high altitude. Med Sci Sports Exerc 2005; 37: 768–74

    Article  PubMed  CAS  Google Scholar 

  185. Pyne DV, McDonald WA, Morton DS, et al. Inhibition of interferon, cytokine, and lymphocyte proliferative responses in elite swimmers with altitude exposure. J Interferon Cytokine Res 2000; 20: 411–8

    Article  PubMed  CAS  Google Scholar 

  186. Biselli R, Le Moli S, Matricardi PM, et al. The effects of hypobaric hypoxia on specific B cell responses following immunization in mice and humans. Aviat Space Environ Med 1991; 62: 870–4

    PubMed  CAS  Google Scholar 

  187. Lancaster GI, Khan Q, Drysdale PT, et al. 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 2004; 98: 565–71

    Article  PubMed  CAS  Google Scholar 

  188. Steensberg A, Toft AD, Bruunsgaard H, et al. Strenuous exercise decreases the percentage of type 1 T cells in the circulation. J Appl Physiol 2001; 91: 1708–12

    PubMed  CAS  Google Scholar 

  189. Kleessen B, Schroedl W, Stueck M, et al. Microbial and immunological responses relative to high-altitude exposure in mountaineers. Med Sci Sports Exerc 2005; 37: 1313–8

    Article  PubMed  Google Scholar 

  190. Bailey DM, Davies B. Physiological implications of altitude training for endurance performance at sea level: a review. Br J Sports Med 1997; 31: 183–90

    Article  PubMed  CAS  Google Scholar 

  191. Mazzeo RS. Altitude, exercise and immune function. Exerc Immunol Rev 2005; 11: 6–16

    PubMed  Google Scholar 

  192. Pedersen BK, Steensberg A. Exercise and hypoxia: effects on leukocytes and interleukin-6-shared mechanisms? Med Sci Sports Exerc 2002; 34: 2004–13

    Article  PubMed  CAS  Google Scholar 

  193. Klokker M, Kjaer M, Secher NH, et al. Natural killer cell response to exercise in humans: effect of hypoxia and epidural anesthesia. J Appl Physiol 1995; 78: 709–16

    Article  PubMed  CAS  Google Scholar 

  194. Chouker A, Demetz F, Martignoni A, et al. Strenuous physical exercise inhibits granulocyte activation induced by high altitude. J Appl Physiol 2005; 98: 640–7

    Article  PubMed  Google Scholar 

  195. Levine BD, Stray-Gundersen J. ‘Living high-training low’: effect of moderate-altitude acclimatization with low-altitude training on performance. J Appl Physiol 1997; 83: 102–12

    PubMed  CAS  Google Scholar 

  196. Tiollier E, Schmitt L, Burnat P, et al. Living high-training low altitude training: effects on mucosal immunity. Eur J Appl Physiol 2005; 94: 298–304

    Article  PubMed  CAS  Google Scholar 

  197. Fox PC, van der Ven PF, Sonies BC, et al. Xerostomia: evaluation of a symptom with increasing significance. J Am Dent Assoc 1985; 110: 519–25

    PubMed  CAS  Google Scholar 

  198. Gleeson M, McDonald WA, Pyne DB, et al. Salivary IgA levels and infection risk in elite swimmers. Med Sci Sports Exerc 1999; 31: 67–73

    Article  PubMed  CAS  Google Scholar 

  199. Hanson LA, Bjorkander J, Qxelius VA. Selective IgA deficiency. In: Chandra RK, editor. Primary and secondary immunodeficiency disorders. Edinburgh: Churchill Livingstone, 1983: 62–4

    Google Scholar 

  200. Isaacs D, Webster AD, Valman HB. Immunoglobulin levels and function in pre-school children with recurrent respiratory infections. Clin Exp Immunol 1984; 58: 335–40

    PubMed  CAS  Google Scholar 

  201. Jauchem JR. Environmental stressors during space flight: potential effects on body temperature. Comp Biochem Physiol A 1988; 91: 425–9

    Article  PubMed  CAS  Google Scholar 

  202. Dinges DF. Sleep in space flight: breath easy—sleep less? Am J Respir Crit Care Med 2001; 164: 337–8

    PubMed  CAS  Google Scholar 

  203. Mallis MM, DeRoshia CW. Circadian rhythms, sleep, and performance in space. Aviat Space Environ Med 2005; 76: B94–107

    PubMed  CAS  Google Scholar 

  204. Drummer C, Hesse C, Baisch F, et al. Water and sodium balances and their relation to body mass changes in microgravity. Eur J Clin Invest 2000; 30: 1066–75

    Article  PubMed  CAS  Google Scholar 

  205. Smith SM, Davis-Street JE, Rice BL, et al. Nutritional status assessment in semiclosed environments: ground-based and space flight studies in humans. J Nutr 2001; 131: 2053–61

    PubMed  CAS  Google Scholar 

  206. Endler NS. The joint effects of person and situation factors on stress in spaceflight. Aviat Space Environ Med 2004; 75: C22–7

    PubMed  Google Scholar 

  207. Durnova GN, Kaplansky AS, Portugalov VV. Effect of a 22-day space flight on the lymphoid organs of rats. Aviat Space Environ Med 1976; 47: 588–91

    PubMed  CAS  Google Scholar 

  208. Sonnenfeld G. The immune system in space and microgravity. Med Sci Sports Exerc 2002; 34: 2021–7

    Article  PubMed  CAS  Google Scholar 

  209. Taylor GR. Overview of spaceflight immunology studies. J Leukoc Biol 1993; 54: 179–88

    PubMed  CAS  Google Scholar 

  210. Taylor GR. Immune changes during short-duration missions. J Leukoc Biol 1993; 54: 202–8

    PubMed  CAS  Google Scholar 

  211. Taylor GR, Dardano JR. Human cellular immune responsiveness following space flight. Aviat Space Environ Med 1983; 54: S55–9

    PubMed  CAS  Google Scholar 

  212. Taylor GR, Neale LS, Dardano JR. Immunological analyses of U.S. Space Shuttle crewmembers. Aviat Space Environ Med 1986; 57: 213–7

    PubMed  CAS  Google Scholar 

  213. Barger LK, Greenleaf JE, Baldini F, et al. Effects of space missions on the human immune system: a meta-analysis. Sports Med Training Rehab 1995; 5: 293–310

    Article  Google Scholar 

  214. Borchers AT, Keen CL, Gershwin ME. Microgravity and immune responsiveness: implications for space travel. Nutrition 2002; 18: 889–98

    Article  PubMed  Google Scholar 

  215. Lange RD, Andrews RB, Gibson LA, et al. Hematological measurements in rats flown on Spacelab shuttle, SL-3. Am J Physiol 1987; 252: R216–21

    PubMed  CAS  Google Scholar 

  216. Sams CF, Crucian BE, Clift VL, et al. Development of a whole blood staining device for use during space shuttle flights. Cytometry 1999; 37: 74–80

    Article  PubMed  CAS  Google Scholar 

  217. Macho L, Kvetnansky R, Fickova M, et al. Endocrine responses to space flights. J Gravit Physiol 2001; 8: 117–20

    Google Scholar 

  218. Tipton CM, Greenleaf JE, Jackson CG. Neuroendocrine and immune system responses with spaceflights. Med Sci Sports Exerc 1996; 28: 988–98

    Article  PubMed  CAS  Google Scholar 

  219. Cogoli A. Space flight and the immune system. Vaccine 1993; 11: 496–503

    Article  PubMed  CAS  Google Scholar 

  220. Konstantinova IV. Immune resistance of man in space flights. Acta Astronaut 1991; 23: 123–7

    Article  PubMed  CAS  Google Scholar 

  221. Chapes SK, Morrison DR, Guikema JA, et al. Production and action of cytokines in space. Adv Space Res 1994; 14: 5–9

    Article  PubMed  CAS  Google Scholar 

  222. Manie S, Konstantinova I, Breittmayer JP, et al. Effects of long duration spaceflight on human T lymphocyte and monocyte activity. Aviat Space Environ Med 1991; 62: 1153–8

    PubMed  CAS  Google Scholar 

  223. Talas M, Batkai L, Stoger I, et al. Results of space experiment program ‘Interferon’. I. Production of interferon in vitro by human lymphocytes aboard space laboratory Solyut-6 (‘Interferon I’) and influence of space flight on lymphocyte functions of cosmonauts (‘Interferon III’). Acta Microbiol Hung 1983; 30: 53–61

    CAS  Google Scholar 

  224. Gould CL, Lyte M, Williams J, et al. Inhibited interferon-gamma but normal interleukin-3 production from rats flown on the space shuttle. Aviat Space Environ Med 1987; 58: 983–6

    PubMed  CAS  Google Scholar 

  225. Konstantinova IV, Rykova MP, Lesnyak AT, et al. Immune changes during long-duration missions. J Leukoc Biol 1993; 54: 189–201

    PubMed  CAS  Google Scholar 

  226. Meshkov D, Rykova M. The natural cytotoxicity in cosmonauts on board space stations. Acta Astronaut 1995; 36: 719–26

    Article  PubMed  CAS  Google Scholar 

  227. Taylor GR, Janney RP. In vivo testing confirms a blunting of the human cell-mediated immune mechanism during space flight. J Leukoc Biol 1992; 51: 129–32

    PubMed  CAS  Google Scholar 

  228. Gmunder FK, Konstantinova I, Cogoli A, et al. Cellular immunity in cosmonauts during long duration spaceflight on board the orbital MIR station. Aviat Space Environ Med 1994; 65: 419–23

    PubMed  CAS  Google Scholar 

  229. Sonnenfeld G. Extreme environments and the immune system: effects of spaceflight on immune responses. J Allergy Clin Immunol 2001; 107: 19–20

    Article  PubMed  CAS  Google Scholar 

  230. Castellani JW. Symposium: immune function in environmental extremes — an introduction. Med Sci Sports Exerc 2002; 34: 2002–3

    Article  PubMed  Google Scholar 

  231. Nickerson CA, Ott CM, Mister SJ, et al. Microgravity as a novel environmental signal affecting Salmonella enterica serovar typhimurium virulence. Infect Immun 2000; 68: 3147–52

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Sport, Health and Exercise Sciences, University of Wales, Bangor, UK

    Neil P. Walsh & Martin Whitham

Authors
  1. Neil P. Walsh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Martin Whitham
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Neil P. Walsh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Walsh, N.P., Whitham, M. Exercising in Environmental Extremes. Sports Med 36, 941–976 (2006). https://doi.org/10.2165/00007256-200636110-00003

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00007256-200636110-00003

Keywords

Search

Navigation