Sports Medicine

, Volume 31, Issue 2, pp 115–144 | Cite as

The Cytokine Response to Physical Activity and Training

  • Andrei I. Moldoveanu
  • Roy J. Shephard
  • Pang N. Shek
Review Article

Abstract

Cytokines are soluble glycoproteins that are produced by and mediate communication between and within immune and nonimmune cells, organs and organ systems throughout the body. Pro- and anti-inflammatory mediators constitute the inflammatory cytokines, which are modulated by various stimuli, including physical activity, trauma and infection. Physical activity affects local and systemic cytokine production at different levels, often exhibiting striking similarity to the cytokine response to trauma and infection.

The present review examines the cytokine response to short term exercise stress, with an emphasis on the balance between pro- and anti-inflammatory mechanisms and modulation of both innate and specific immune parameters through cytokine regulation. The effects of long term exercise on cytokine responses and the possible impact on various facets of the immune system are also discussed, with reference to both cross-sectional and longitudinal studies of exercise training. Finally, the validity of using exercise as a model for trauma and sepsis is scrutinised in the light of physiological changes, symptomatology and outcome, and limitations of the model are addressed.

Further studies, examining the effect of exercise, trauma and infection on novel cytokines and cytokine systems are needed to elucidate the significance of cytokine regulation by physical activity and, more importantly, to clarify the health implications of short and long term physical activity with respect to overall immune function and resistance to infection.

Notes

Acknowledgements

The research of Dr Shephard is supported in part by a grant from the Defence and Civil Institute of Environmental Medicine.

References

  1. 1.
    Shephard RJ, Shek PN. Physical activity and immune changes: a potential model of subclinical inflammation and sepsis. Crit Rev Rehab Phys Med 1996; 8 (3): 153–81Google Scholar
  2. 2.
    Rhind SG, Shek PN, Shephard RJ. The impact of exercise on cytokines and receptor expression. Exerc Immunol Rev 1995; 1: 97–148Google Scholar
  3. 3.
    Northoff H, Enkel S, Weinstock C. Exercise, injury and immune function. Exerc Immunol Rev 1995; 1: 1–25Google Scholar
  4. 4.
    Shephard RJ, Shek PN. Immune responses to inflammation and trauma: a physical training model. Can J Physiol Pharmacol 1998; 76: 469–72PubMedCrossRefGoogle Scholar
  5. 5.
    Kuby J. Cytokines. In: Immunology. 2nd ed. New York: W.H. Freeman and Co., 1994: 297–322Google Scholar
  6. 6.
    Dinarello CA. The biological properties of interleukin-1. Eur Cytokine Netw 1994; 5 (6): 517–31PubMedGoogle Scholar
  7. 7.
    Kostura MJ, Tocci MJ, Limjuco G, et al. Identification of monocyte specific pre-interleukin 1 beta convertase activity. Proc Natl Acad Sci USA 1989; 86: 5227–31PubMedCrossRefGoogle Scholar
  8. 8.
    Lennard AC. Interleukin-1 receptor antagonist. Crit Rev Immunol 1995; 15: 77–105PubMedCrossRefGoogle Scholar
  9. 9.
    Bertini R, Bianchi M, Ghezzi P. Adrenalectomy sensitizes mice to the lethal effects of interleukin 1 and tumor necrosis factor. J Exp Med 1988; 167: 1708–12PubMedCrossRefGoogle Scholar
  10. 10.
    Beasley D, Cohen RA, Levinsky NG. Interleukin 1 inhibits contraction of vascular smooth muscle. J Clin Invest 1989; 83: 331–5PubMedCrossRefGoogle Scholar
  11. 11.
    Beasley D, Schwartz JH, Brenner BM. Interleukin-1 induces prolonged L-arginine-dependent cyclic guanosine monophosphate and nitrite production in rat vascular smooth muscle cells. J Clin Invest 1991; 87: 602–8PubMedCrossRefGoogle Scholar
  12. 12.
    Gulick T, Chung MK, Pieper SJ, et al. Interleukin 1 and tumor necrosis factor inhibit cardiac myocyte beta-adrenergic responsiveness. Proc Natl Acad Sci USA 1989; 86: 6753–7PubMedCrossRefGoogle Scholar
  13. 13.
    Coceani F, Lees J, Dinarello CA. Occurrence of interleukin 1 in cerebrospinal fluid of the conscious cat. Brain Res 1988; 446: 245–50PubMedCrossRefGoogle Scholar
  14. 14.
    Konig A, Muhlbauer RC, Fleisch H. Tumor necrosis factor and interleukin 1 stimulate bone resorption in vivo as measured by [3-H] tetracycline excretion from prelabeled mice. J Bone Miner Res 1988; 3: 621–7PubMedCrossRefGoogle Scholar
  15. 15.
    Zamir O, Hasselgren PO, O’Brien W et al. Muscle protein breakdown during endotoxemia in rats before and after treatment with interleukin-1 receptor antagonist (IL-1ra). Ann Surg 1992; 216: 381–5PubMedCrossRefGoogle Scholar
  16. 16.
    Fibbe WE, Falkenburn JHF. Regulation of hematopoiesis by interleukin-1. Biotherapy 1990; 2: 325–35PubMedCrossRefGoogle Scholar
  17. 17.
    Simic MM, Stocic-Grujicic S. The dual role of interleukin-1 in lectin-induced proliferation of T cells. Folia Biol 1985; 31: 410–24Google Scholar
  18. 18.
    Dejana E, Bertocchi F, Bortolami MC, et al. Interleukin-1 promotes tumor cell adhesion to cultured human endothelial cells. J Clin Invest 1988; 82: 1466–70PubMedCrossRefGoogle Scholar
  19. 19.
    Coceani F, Lees J, Reford J, et al. Interleukin-1 receptor antagonist: effectiveness against interleukin-1 fever. J Physiol Pharmacol 1992; 7: 1590–6CrossRefGoogle Scholar
  20. 20.
    Kammuler ME. Recombinant human interleukin-6: safety issues of a pleiotropic growth factor. Toxicology 1995; 105: 91–107CrossRefGoogle Scholar
  21. 21.
    Ndubuisi MI, Patel K, Rayanade RJ, et al. Distinct classes of chaperoned IL-6 in human blood: differential immunological and biological activity. J Immunol 1998; 160: 494–501PubMedGoogle Scholar
  22. 22.
    Simpson RJ, Hammacher A, Smith DK, et al. Interleukin-6: structure-function relationships. Protein Sci 1997; 6: 929–55PubMedCrossRefGoogle Scholar
  23. 23.
    Cohen MC, Cohen S. Cytokine function: a study in biologic diversity. Am J Clin Pathol 1996; 105: 589–98PubMedGoogle Scholar
  24. 24.
    Baumann H, Gauldie J. The acute phase response. Immunol Today 1994; 15: 74–80PubMedCrossRefGoogle Scholar
  25. 25.
    Crane LJ, Miller DL. Plasma protein induction by isolated hepatocytes. Mol Cell Biochem 1983; 53/54: 89–109PubMedGoogle Scholar
  26. 26.
    Asano S, Okano A, Ozawa K. In vivo effects of recombinant interleukin-6 in primates: stimulated production of platelets. Blood 1990; 75: 1602–5PubMedGoogle Scholar
  27. 27.
    Hirano T. Interleukin-6 and its relation to inflammation and disease. Clin Immunol Immunopathol 1992; 62: 60–5CrossRefGoogle Scholar
  28. 28.
    Hirano T, Akira S, Taga T, et al. Biological and clinical aspects of interleukin 6. Immunol Today 11: 443–8Google Scholar
  29. 29.
    Linker-Israeli M, Deans RJ, Wallace RJ, et al. Elevated levels of endogenous IL-6 in systemic lupus erythromatosus: a putative role in pathogenesis. J Immunol 1991; 147: 117–23PubMedGoogle Scholar
  30. 30.
    Tilg H, Trehu E, Atkins MB, et al. Interleukin-6 (IL-6) as an anti-inflammatory cytokine: induction of circulating IL-1 receptor antagonist and soluble tumor necrosis factor p55. Blood 1994; 83: 113–8PubMedGoogle Scholar
  31. 31.
    Hirano T, Matsuda T, Nakajima K. Signal transduction through gp130 that is shared among the receptors for the interleukin 6 related cytokine subfamily. Stem Cells 1994; 12: 262–77PubMedCrossRefGoogle Scholar
  32. 32.
    Pennica D, Nedwin GE, Hayflick JS. Human tumor necrosis factor: precursor structure, expression, and homology to lymphotoxin. Nature 1984; 312: 724–9PubMedCrossRefGoogle Scholar
  33. 33.
    Bemelmans MHA, van Tits LJH, Buurman WA. Tumor necrosis factor: function, release and clearance. Crit Rev Immunol 1996; 16: 1–11PubMedCrossRefGoogle Scholar
  34. 34.
    Rowsey PJ, Borer KT, Kluger MJ. Tumor necrosis factor is not involved in exercise-induced elevation in core temperature. Am J Physiol 1993; 265 (6 Pt 1): R1351–4Google Scholar
  35. 35.
    Long NC, Vander AJ, Kunkel SL, et al. Antiserum against tumor necrosis factor increases stress hyperthermia in rats. Am J Physiol 1990; 258 (3 Pt 2): R591–5Google Scholar
  36. 36.
    Bender BA, Milsark IA, Cerami A. Cachectin/tumor necrosis factor: production, distribution, and metabolic fate. J Immunol 1985; 135: 3972–7Google Scholar
  37. 37.
    Aderka D, Engelmann H, Maor Y, et al. Stabilization of the bioactivity of tumor necrosis factor by its soluble receptors. J Exp Med 1992; 175: 323–9PubMedCrossRefGoogle Scholar
  38. 38.
    Farrar MA, Schreiber RD. The molecular cell biology of interferon-gamma and its receptor. Annu Rev Immunol 1993; 11: 571–611PubMedCrossRefGoogle Scholar
  39. 39.
    Derynck R, Leung D, Gray P, et al. Human interferon is encoded by a single class of mRNA. Nucleic Acids Res 1982; 10: 3605–15PubMedCrossRefGoogle Scholar
  40. 40.
    Billiau A. Interferon gamma: biology and role in pathogenesis. Adv Immunol 1996; 62: 61–130PubMedCrossRefGoogle Scholar
  41. 41.
    Mantovani A, Dejana E. Cytokines as communication signals between leukocytes and endothelial cells. Immunol Today 1989; 10: 370–5PubMedCrossRefGoogle Scholar
  42. 42.
    Ortaldo JR. Regulation of natural killer activity. Cancer Metastasis Rev 1987; 6: 637–51PubMedCrossRefGoogle Scholar
  43. 43.
    Reiter Z. Interferon: a major regulator of natural killer cell-mediated cytotoxicity. J Interferon Res 1993; 13: 247–57PubMedCrossRefGoogle Scholar
  44. 44.
    Young HA. Regulation of interferon-gamma gene expression. J Interferon Res 1996; 16: 563–8CrossRefGoogle Scholar
  45. 45.
    Ruggiero V, Tavernier J, Fiers W, et al. Induction of synthesis of tumor necrosis factor alpha by interferon gamma. J Immunol 1986; 136: 2445–50PubMedGoogle Scholar
  46. 46.
    Lowenstein CJ, Snyder SH. Nitric oxide, a novel biologic messenger. Cell 1992; 70: 705–7PubMedCrossRefGoogle Scholar
  47. 47.
    Gresser I. Biological effects of interferons. J Invest Dermatol 1990; 95: 66S-71SCrossRefGoogle Scholar
  48. 48.
    Gilman-Sachs A, DuChateau B. Clinical relevance of chemokines [abstract]. Clin Immunol Newsl 1997; 17 (7): 93CrossRefGoogle Scholar
  49. 49.
    Malkovsky M, Sondel PM. Interleukin 2 and its receptor: structure, function and therapeutic potential. Blood Rev 1987; 1: 254–66PubMedCrossRefGoogle Scholar
  50. 50.
    Lai KN, Leung JCK, Lai FM. Soluble IL-2 receptor release, interleukin 2 production, and interleukin 2 receptor expression in activated T -lymphocytes. Pathology 1991; 23: 224–8PubMedCrossRefGoogle Scholar
  51. 51.
    Rubin LA, Nelson DL. The soluble interleukin-2 receptor: biology, function, and clinical application. Ann Intern Med 1990; 113: 619–27PubMedGoogle Scholar
  52. 52.
    Taga K, Kasahara Y, Yachie A, et al. Preferential expression of IL-2 receptor subunits on memory populations within CD4+ and CD8+T cells. Immunology 1991; 72: 15–9PubMedGoogle Scholar
  53. 53.
    Sheldon A, Flego L, Zola H. Coexpression of IL-2 receptor p55 and p75 by circulating blood lymphocytes. J Leuk Biol 1993; 54: 161–6Google Scholar
  54. 54.
    Aribia M-HB, Moire N, Metivier D, et al. IL-2 receptors on circulating natural killer cells and T lymphocytes. J Immunol 1989; 142: 490–9PubMedGoogle Scholar
  55. 55.
    Nagler A, Lanier LL, Phillips JH. Constitutive expression of high affinity interleukin 2 receptors on human CD 16-natural killer cells in vivo. J Exp Med 1990; 171: 1527–33PubMedCrossRefGoogle Scholar
  56. 56.
    Scheibenbogen C, Keilholtz U, Richter M, et al. The interleukin-2 receptor in human monocytes and macrophages: regulation of expression and release of the α and β chains (p55 and p75). Res Immunol 1992; 143: 33–7PubMedCrossRefGoogle Scholar
  57. 57.
    Tsudo M, Uchiyama T, Uchino H. Expression of the Tac antigen on activated normal human B cells. J Exp Med 1984; 160: 612–7PubMedCrossRefGoogle Scholar
  58. 58.
    Doherty TM, Seder RA, Sher A. Induction and regulation of IL-15 expression in murine macrophages. J Immunol 1996; 156:735–41PubMedGoogle Scholar
  59. 59.
    Giri JG, Ahdieh J, Eisenman K, et al. Utilization of the beta and gamma chains of the interleukin-2 (IL-2) receptor by the novel cytokine IL-15. EMBO J 1994; 13: 2822–30PubMedGoogle Scholar
  60. 60.
    Baggiolini M, Dewald B, Moser B. Human chemokines: an update. Annu Rev Immunol 1997; 15: 675–705PubMedCrossRefGoogle Scholar
  61. 61.
    Greenberg MJ, Streiter RM, Kunkel SL, et al. Neutralization of macrophage inflammatory protein-2 attenuates neutrophil recruitment and bacterial clearance in murine Klebsiella pneumonia. J Infect Dis 1996; 173: 173–59Google Scholar
  62. 62.
    Strieter RM, Koch AE, Antony VB, et al. The immunopathology of chemotactic chemokines: the role of interleukin-8 and monocyte chemoattractant protein-1. J Lab Clin Med 1994; 123: 183–97PubMedGoogle Scholar
  63. 63.
    Gong J-H, Clark-Lewis I. Antagonists of monocyte chemoattractant protein-1 identified by modification of functionally critical NH2-terminal residues. J Exp Med 1995; 181: 631–40PubMedCrossRefGoogle Scholar
  64. 64.
    Kluth DC, Rees AJ. Inhibiting inflammatory cytokines. Semin Nephrol 1996; 16 (6): 576–82PubMedGoogle Scholar
  65. 65.
    Brown MA, Hural J. Functions of IL-4 and control of its expression. Crit Rev Immunol 1997; 17: 1–32PubMedCrossRefGoogle Scholar
  66. 66.
    Colotta F, Re F, Muzio M. Interleukin-13 (IL-13) induces expression and release of interleukin-1 (IL-1) decoy receptor in human polymorphonuclear cells. J Biol Chem 1994; 269: 12403–6PubMedGoogle Scholar
  67. 67.
    Te Velde A, Huijbens RJF, de Vries JE. IL-4 increases FcγRc membrane expression and FcγRc-mediated cytotoxic activity of human monocytes. J Immunol 1990; 144: 3046–51Google Scholar
  68. 68.
    de Vries JE, Zurawski G. Immunoregulatory properties of IL-13: its potential role in atopic disease. Int Arch Allergy Immunol 1995; 106: 175–9PubMedCrossRefGoogle Scholar
  69. 69.
    Zurawski G, de Vries JE. Interleukin 13, an interleukin-4-like cytokine that acts on monocytes and B-cells, but not T-cells. Immunol Today 1994; 15: 19–26PubMedCrossRefGoogle Scholar
  70. 70.
    Schindler R, Clark RD, Dinarello CA. Dissociation between interleukin-1β mRNA and protein synthesis in human peripheral blood mononuclear cells. J Biol Chem 1990; 265: 10232–7PubMedGoogle Scholar
  71. 71.
    Bogdan C, Nathan C. Modulation of macrophage function by transforming growth factor R, interleukin-4 and interleukin 10. Proc Natl Acad Sci 1993; 685: 713–39CrossRefGoogle Scholar
  72. 72.
    Joyce DA, Gibbons DP, Green P. Two inhibitors of inflammatory cytokine release, interleukin 10 and interleukin 4, have contrasting effects on the release of soluble p75 tumor necro sis factor receptor by cultured monocytes. Eur J Immunol 1994; 24: 2699–705PubMedCrossRefGoogle Scholar
  73. 73.
    Burdin N, Rousset F, Banchereau J. B-cell-derived IL-10: production and function. Methods 1997; 11: 98–111PubMedCrossRefGoogle Scholar
  74. 74.
    Malefyt RW, Yssel H, Roncarolo M-G, et al. Interleukin-10. Curr Opin Immunol 1992; 4: 314–20CrossRefGoogle Scholar
  75. 75.
    Pedersen BK, Ostrowski K, Rohde T, et al. The cytokine response to strenuous exercise. Can J Physiol Pharmacol 1998; 76: 505–11PubMedCrossRefGoogle Scholar
  76. 76.
    Brenner IKM, Natale VM, Suntres ZE, et al. Impact of different types of exercise on components of the inflammatory response [abstract]. Med Sci Sports Exerc 1998; 30 (5 Suppl.): S 19Google Scholar
  77. 77.
    Brenner IKM, Natale VM, Vasiliou P, et al. Impact of three different types of exercise on components of the inflammatory response. Eur J Appl Physiol 1999; 80: 452–60CrossRefGoogle Scholar
  78. 78.
    Bruunsgaard H, Galbo H, Halkjaer-Kristensen J, et al. Exercise-induced increase in serum interleukin-6 in humans is related to muscle damage. J Physiol (Lond) 1997; 499: 833–41Google Scholar
  79. 79.
    Nieman DC, Nehlsen-Cannarella SL, Fagoaga OR, et al. Influence of mode and carbohydrate on the cytokine response to heavy exertion. Med Sci Sports Exerc 1998; 30: 671–8PubMedCrossRefGoogle Scholar
  80. 80.
    Gannon GA, Rhind SG, Slick PN, et al. Inhibition of exercise-induced cytokine release by thermal clamping [abstract]. FASEB J 2000; 14: A619Google Scholar
  81. 81.
    Moldoveanu AI, Shephard RJ, Slick PN. Prolonged exercise elevates plasma levels but not gene expression of IL-1 β, IL-6, and TNFα, in circulating mononuclear cells. J Appl Physiol 2000; 89: 1499–504PubMedGoogle Scholar
  82. 82.
    Rhind SG, Slick PN, Brenner IKM, et al. Intracellular and serum cytokine profiles after 8 days of exhaustive exercise and cold exposure [abstract]. FASEB J 2000; 14: A618Google Scholar
  83. 83.
    Haahr PM, Pedersen BK, Fomsgaard A, et al. Effect of physical exercise on in vitro production of interleukin 1, interleukin 6, tumor necrosis factor-α, interleukin 2 and interferon-gamma. Int J Sports Med 1991; 12: 223–7PubMedCrossRefGoogle Scholar
  84. 84.
    Fielding R, Manfredi T, Ding W et al. Prolonged alterations in skeletal muscle ultrastructure following eccentric exercise. Clin Sci 1994; 87 Suppl.: 82–3Google Scholar
  85. 85.
    Ostrowski K, Rohde T, Asp S, et al. The sequential release of cytokines in strenuous exercise. Int J Sports Med 1998; 19 Suppl. 3: S216–7Google Scholar
  86. 86.
    Cannon JG, Fielding RA, Fiatarone MA, et al. Increased interleukin 1β in human skeletal muscle after exercise. Am J Physiol 1989; 257 (2 Pt 2): R451–5Google Scholar
  87. 87.
    Netea MG, Drenth JPH, De Bout N, et al. A semi-quantitative reverse transcriptase polymerase chain reaction method for measurement of mRNA for TNF-alpha and IL-1beta in whole blood cultures: its application in typhoid fever and eccentric exercise. Cytokine 1996; 8 (9): 739–44PubMedCrossRefGoogle Scholar
  88. 88.
    Ullum H, Haahr PM, Diamant M, et al. Bicycle exercise enhances plasma IL-6 but does not change IL-1α, IL-6, or TNF-α pre-mRNA in BMNC. J Appl Physiol 1994; 77: 93–7PubMedGoogle Scholar
  89. 89.
    Ostrowski K, Rohde T, Zacho M, et al. Evidence that interleukin-6 is produced in human skeletal muscle during prolonged running. J Physiol (Lond) 1998; 508: 949–53CrossRefGoogle Scholar
  90. 90.
    Natelson BH, Zhou X, Ottenweller JE, et al. Effect of acute exhausting exercise on cytokine gene expression in men. Int J Sports Med 1996; 17: 299–302PubMedCrossRefGoogle Scholar
  91. 91.
    Anwar A, Smith LL, Holbert D, et al. Serum cytokines after strenuous exercise [abstract]. Med Sci Sports Exerc 1997; 29 Suppl.: S73Google Scholar
  92. 92.
    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 vivo. Int J Sports Med 1988; 9: 114–7PubMedCrossRefGoogle Scholar
  93. 93.
    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: 281–7PubMedCrossRefGoogle Scholar
  94. 94.
    Weinstock C, Konig D, Harnischmacher R, et al. Effect of exhaustive exercise on the cytokine response. Med Sci Sports Exerc 1997; 29: 345–54PubMedCrossRefGoogle Scholar
  95. 95.
    Sprenger H, Jacobs C, Nain M, et al. Enhanced release of cytokines, interleukin-2 receptors and neopterin after long-distance running. Clin Immunol Immunopathol 1992; 63: 188–95PubMedCrossRefGoogle Scholar
  96. 96.
    Bury TB, Louis R, Radennecker ME, et al. Blood mononuclear cells mobilization and cytokine secretion during prolonged exercises. Int J Sports Med 1996; 17: 156–60PubMedCrossRefGoogle Scholar
  97. 97.
    Woods JA, Linner KM, Sharp BM. Effects of exhaustive exercise on LPS-induced IL-6 gene expression [abstract]. Med Sci Sports Exerc 1997; 26 (5 Suppl.): S 182Google Scholar
  98. 98.
    Nehlsen-Cannarella SL, Fagoaga OR, Nieman DC, et al. Carbohydrate and cytokine response to 2.5 h of running. J Appl Physiol 1997; 82: 1662–7PubMedGoogle Scholar
  99. 99.
    Papanicolaou DA, Pestrides JS, Tsigos C, et al. Exercise stimulates interleukin-6 secretion: inhibition by glucocorticoids and correlation with catecholamines. Am J Physiol 1996; 271 (3 Pt 1): E601–5Google Scholar
  100. 100.
    Rivier A, Pene J, Chanez P, et al. Release of cytokines by blood monocytes during strenuous exercise. Int J Sports Med 1994; 15: 192–8PubMedCrossRefGoogle Scholar
  101. 101.
    Gannon GA, Rhind SG, Suzui M, et al. Changes in selected cellular and soluble mediators of immunity following a 250.5 km competitive road-cycling race. Proceedings, International Society of Exercise Immunology; 1995 Nov; Brussels, 40Google Scholar
  102. 102.
    Gannon GA, Rhind SG, Suzui M, et al. Circulating levels of peripheral blood leucocytes and cytokines following competitive cycling. Can J Appl Physiol 1997; 22: 133–47PubMedCrossRefGoogle Scholar
  103. 103.
    Northoff H, Berg A. Immunologic mediators as parameters of the reaction to strenuous exercise. Int J Sports Med 1991; 12: 9–15CrossRefGoogle Scholar
  104. 104.
    Suzuki K, Totsuka M, Nakaji M, et al. Endurance exercise causes interactions among stress hormones, cytokines, neutrophil dynamics, and muscle damage. J Appl Physiol 1999; 87: 1360–7PubMedGoogle Scholar
  105. 105.
    Rokitzki L, Logemann E, Keul J. Interleukin-6, tumor necrosis factor-alpha and malon-dialdehyde serum concentration during a marathon-run. Int J Sports Med 1994; 15: 360CrossRefGoogle Scholar
  106. 106.
    Dufaux B, Order U. Plasma elastase-αl-antitrypsin, neopterin, tumor necrosis factor, and soluble interleukin-2 receptor after prolonged exercise. Int J Sports Med 1989; 10: 434–8PubMedCrossRefGoogle Scholar
  107. 107.
    Espersen GT, Elbaek A, Ernst E, et al. Effect of physical exercise on cytokines and lymphocyte subpopulations in human peripheral blood. APMIS 1990; 98: 395–400PubMedCrossRefGoogle Scholar
  108. 108.
    Baum M, Muller-Steinhardt M, Liesen H, et al. Moderate and exhaustive endurance exercise influences the interferon-gamma levels in whole-blood culture supernatants. Eur J Appl Physiol 1997; 76: 165–9CrossRefGoogle Scholar
  109. 109.
    Bagby GJ, Sawaya DE, Crouch LD, et al. Prior exercise suppresses the plasma tumor necrosis factor response to bacterial lipopolysaccharide. J Appl Physiol 1994; 77: 1542–7PubMedGoogle Scholar
  110. 110.
    Drenth JPH, van Uun SHM, van Demen M, et al. Endurance run increases circulating IL-6 and IL-1ra but downregulates ex vivo TNF-α and IL-1β production. J Appl Physiol 1995; 79: 1497–503PubMedGoogle Scholar
  111. 111.
    Drenth JPH, Krebbers RJM, Bijzet J, et al. Increased circulating cytokine receptors and ex vivo interleukin-1 receptor antagonist and interleukin-1beta but decreased tumor necrosis factor-alpha production after a 5-km run. Eur J Clin Invest 1998; 28: 866–72PubMedCrossRefGoogle Scholar
  112. 112.
    Northoff H, Weinstock C, Berg A. The cytokine response to strenuous exercise. Int J Sports Med 1994; 15 Suppl. 3: S167–71CrossRefGoogle Scholar
  113. 113.
    Ostrowski K, Rohde T, Asp S, et al. Pro- and anti-inflammatory cytokine balance in strenuous exercise in humans. J Physiol (Lond) 1999; 515: 287–91CrossRefGoogle Scholar
  114. 114.
    Sutton BJ, Gould HJ. The human IgE network. Nature 1993; 366: 421–8PubMedCrossRefGoogle Scholar
  115. 115.
    Moyna NM, Acker GR, Fulton JR, et al. Lymphocyte function and cytokine production during incremental exercise in active and sedentary males and females. Int J Sports Med 1996; 17: 585–91PubMedCrossRefGoogle Scholar
  116. 116.
    Castell L, Poortmans JR, Leclercq R, et al. Some aspects of the acute phase response after a marathon race. Eur J Appl Physiol 1997; 75: 47–53CrossRefGoogle Scholar
  117. 117.
    Smith JA, Telford RD, Baker MS, et al. Cytokine immunoreactivity in plasma does not change after moderate endurance exercise. J Appl Physiol 1992; 73: 1396–401PubMedGoogle Scholar
  118. 118.
    Camus G, Poortmans J, Nys M, et al. Mild endotoxemia and the inflammatory response induced by a marathon race. Clin Sci 1997; 92: 415–22PubMedGoogle Scholar
  119. 119.
    Northoff H, Flegel W, Männel DN, et al. Increased levels of interleukin-6 (IL-6) and/or IL-7 in sera of long-distance runners. In: Dinarello C, Kluger ML, Powanda MC, etal., editors. The physiological and pathological effects of cytokines. New York (NY): Wiley-Liss, Inc., 1990: 75–9Google Scholar
  120. 120.
    Fitzpatrick DR, Shirley KM, McDonald LE, et al. Distinct methylation of the interferon gamma (IFN-gamma) and interleukin 3 (IL-3) genes in newly activated primary CD8+ T lymphocytes: regional IFN-gamma promoter demethylation and mRNA expression are heritable in CD44(high)CD8+ T cells. J Exp Med 1998; 188: 103–17PubMedCrossRefGoogle Scholar
  121. 121.
    Umland SP, Razac S, Shah H, et al. Interleukin-5 mRNA stability in human T cells is regulated differently than interleukin-2, interleukin-3, interleukin-4, granulocyte/macrophage colony stimulating factor, and interferon gamma. Am J Respir Cell Mol Biol 1998; 18: 631–42PubMedGoogle Scholar
  122. 122.
    Mann DL. Stress activated cytokines and the heart. Cytokine Growth Factor Rev 1996; 7: 341–54PubMedCrossRefGoogle Scholar
  123. 123.
    Turnbull AV, Rivier CL. Regulation of the hypothalamic-pituitary-adrenal axis by cytokines: actions and mechanisms of action. Physiol Rev 1999; 79: 1–71PubMedGoogle Scholar
  124. 124.
    Rhind SG, Slick PN, Shinkai S, et al. Effects of moderate endurance exercise and training on in vitro lymphocyte proliferation, interleukin-2 (IL-2) production, and IL-2 receptor expression. Eur J Appl Physiol 1996; 64: 348–60CrossRefGoogle Scholar
  125. 125.
    Nasrullah I, Mazzeo RS. Age-related immunosenescence in Fischer 344 rats: influence of exercise training. J Appl Physiol 1992;73:1932–8PubMedGoogle Scholar
  126. 126.
    Gmünder FK, Joller PW, Joller-Jemelka HI, et al. Effect of a herbal yeast food supplement and long-distance running on immunological parameters. Br J Sports Med 1990; 24: 103–12PubMedCrossRefGoogle Scholar
  127. 127.
    Fry RW, Morton AR, Crawford GMP, et al. Cell numbers and in-vitro responses of leukocytes and lymphocyte subpopulations following maximal exercise and interval training sessions of different intensities. Eur J Appl Physiol 1992; 64: 218–27CrossRefGoogle Scholar
  128. 128.
    Tilz GP, Domej W, Diez-Ruiz A, et al. Increased immune activation during and after physical exercise. Immunobiology 1993; 188: 194–202PubMedCrossRefGoogle Scholar
  129. 129.
    Gray AB, Smart YC, Telford RD, et al. Anaerobic exercise causes transient changes in leukocyte subsets and IL-2R expression. Med Sci Sports Exerc 1992; 24: 1332–8PubMedGoogle Scholar
  130. 130.
    Viti A, Muscatella M, Paulescu L, et al. Effect of exercise on plasma interferon levels. J Appl Physiol 1985; 59: 426–8PubMedGoogle Scholar
  131. 131.
    Smits HH, Grunberg K, Derijk RH, et al. Cytokine release and its modulation by dexamethasone in whole blood following exercise. Clin Exp Immunol 1998; 111 (2): 463–8PubMedCrossRefGoogle Scholar
  132. 132.
    Surkina ID, Danilenko SV, Dudov NS, et al. The role of the immune system in processes of adaptations to stress in sportsmen. Clin Sci 1994; 87 Suppl.: 22Google Scholar
  133. 133.
    Nieman DC. Immune response to heavy exertion. J Appl Physiol 1997; 82: 1385–94PubMedGoogle Scholar
  134. 134.
    Nielsen HB, Hanel B, Loft S, et al. Restricted pulmonary diffusion capacity after exercise is not an ARDS-like injury. J Sports Sci 1995; 13: 109–13PubMedCrossRefGoogle Scholar
  135. 135.
    Hopkins SR, Schoene RB, Henderson WR, et al. Intense exercise impairs the integrity of pulmonary blood-gas barrier in elite athletes. Am J Respir Crit Care Med 1997; 155 (3): 1090–4PubMedGoogle Scholar
  136. 136.
    Ostrowski K, Hermann C, Bangash A, et al. A trauma-like elevation in plasma cytokines in humans in response to treadmill running. J Physiol (Lond) 1998; 513: 889–94CrossRefGoogle Scholar
  137. 137.
    Krishnaswamy G, Smith JK, Srikanth S, et al. Effect of moderate exercise on the TH1 and TH2 cytokine mRNA profiles of circulating lymphocytes. J Allergy Clin Immunol 1997; 95 (1 Pt 2): 359Google Scholar
  138. 138.
    Klava A, Windsor ACJ, Farmery SM, et al. Interleukin-10: A role in the development of postoperative immnunosuppression. Arch Surg 1997; 132: 425–9PubMedCrossRefGoogle Scholar
  139. 139.
    Baum M, Klopping-Menke K, Muller-Steinhardt M, et al. Increased concentrations of interleukin-l-beta in whole blood culture supernatants after 12 weeks of moderate endurance exercise. Eur J Appl Physiol 1999; 79: 500–3CrossRefGoogle Scholar
  140. 140.
    Nieman DC. Exercise, infection and immunity. Int J Sports Med 1994; 15 Suppl.: S131–41Google Scholar
  141. 141.
    Shephard RJ, Shek PN. Potential impact of physical activity and sport on the immune system: a brief review. Br J Sports Med 1994; 28: 247–55PubMedCrossRefGoogle Scholar
  142. 142.
    Shephard RJ, Slick PN. Impact of physical activity and sport on the immune system. Rev Environ Health 1996; 11: 133–47CrossRefGoogle Scholar
  143. 143.
    Shinkai S, Kohno H, Kimura K, et al. Physical activity and immune senescence in men. Med Sci Sports Exerc 1995; 27: 1516–26PubMedGoogle Scholar
  144. 144.
    Baj Z, Kantorski J, Majewska E, et al. Immune status of competitive cyclists before and after the training session. Int J Sports Med 1994; 15: 319–24PubMedCrossRefGoogle Scholar
  145. 145.
    Weicher H, Werle E. Interactions between hormones and the immune system. Int J Sports Med 1991; 12 Suppl.: S30–7Google Scholar
  146. 146.
    Papa S, Vitale M, Mazzoti G, et al. Impaired lymphocyte stimulation induced by long-term training. Immunol Lett 1989; 22: 29–33PubMedCrossRefGoogle Scholar
  147. 147.
    Rhind SG, Shek PN, Shinkai S, et al. Differential expression of interleukin-2 receptor alpha and beta chains in relation to natural killer cell subsets and aerobic fitness. Int J Sports Med 1994; 15: 911–8CrossRefGoogle Scholar
  148. 148.
    Shinkai S, Konishi K, Shephard RJ. Aging, exercise, training and the immune system. Exerc Immunol Rev 1997; 3: 68–95PubMedGoogle Scholar
  149. 149.
    Rall LC, Roubenoff R, Cannon JG, et al. Effects of progressive resistance training on immune response in aging and chronic inflammation. Med Sci Sports Exerc 1996; 28: 1356–65PubMedCrossRefGoogle Scholar
  150. 150.
    Lighart GJ, Corberand JX, Fournier C, et al. Admission criteria for immunogerontological studies in man: the SENIEUR protocol. Mech Ageing Dev 1990; 28: 47–55CrossRefGoogle Scholar
  151. 151.
    Hoffman-Goetz L, Sweeny AL. Lymphokine activated killer cell activity following voluntary physical activity in mice. J Sports Med Phys Fitness 1994; 34: 83–90PubMedGoogle Scholar
  152. 152.
    Foex BA, Shelly MP. The cytokine response to critical illness. J Accid Emerg Med 1996; 13: 154–62PubMedCrossRefGoogle Scholar
  153. 153.
    Kelly JL, O’Sullivan C, O’Riordain M, et al. Is circulating endotoxin the trigger for the systemic inflammatory response syndrome seen after injury. Ann Surg 1997; 225: 530–43PubMedCrossRefGoogle Scholar
  154. 154.
    O’Sullivan S, Lederer JA, Horgan AF, et al. Major injury leads to predominance of the T helper-2 phenotype and diminished interleukin-12 production associated with decreased resistance to infection. Ann Surg 1995; 222: 482–92PubMedGoogle Scholar
  155. 155.
    van Zee KJ, Kohmo T, Fischer E, et al. Tumor necrosis factor soluble receptors circulate during experimental and clinical inflammation and can protect against excessive tumor necro sis factor alpha in vitro and in vivo. Proc Natl Acad Sci USA 1992; 89: 4845–9PubMedCrossRefGoogle Scholar
  156. 156.
    Shek PN, Sabiston BH, Buguet A, et al. Strenuous exercise and immunological changes. Int J Sports Med 1995; 16: 466–74PubMedCrossRefGoogle Scholar
  157. 157.
    Vindenes H, Ulvestad E, Bjerknes R. Increased levels of circulating interleukin-8 in patients with large burns: relation to burn size and sepsis. J Trauma 1995; 39: 635–40PubMedCrossRefGoogle Scholar
  158. 158.
    Armstrong RB, Ogilvie RW, Schwane JA. Eccentric exercise-induced injury to rat skeletal muscle. J Appl Physiol 1983; 54: 80–93PubMedGoogle Scholar
  159. 159.
    Pyne D. Regulation of neutrophil function during exercise. Sports Med 1994; 17: 245–58PubMedCrossRefGoogle Scholar
  160. 160.
    Clarkson PM, Nosaka K, Braun M. Muscle function after exercise-induced muscle damage and rapid adaptation. Med Sci Sports Exerc 1992; 24: 512–20PubMedGoogle Scholar
  161. 161.
    St. Pierre B, Tidball JG. Differential response of macrophage subpopulations to soleus muscle reloading after rat hindlimb suspension. J Appl Physiol 1994; 77: 290–7PubMedGoogle Scholar
  162. 162.
    Newham DJ. The consequences of eccentric contractions and their relationship to delayed onset muscle pain. Eur J Appl Physiol 1988; 57: 353–9CrossRefGoogle Scholar
  163. 163.
    Reid W, Huang J, Byron S. Diaphragm injury and myofibrillar structure induced by resistive loading. J Appl Physiol 1994; 76: 176–84PubMedGoogle Scholar
  164. 164.
    Ayala A, Chaudry IH. Immune dysfunction in murine polymicrobial sepsis: mediators, macrophages, lymphocytes and apoptosis. Shock 1996; 6: S27–38CrossRefGoogle Scholar
  165. 165.
    Bliff WL, Moore FA, Carl VS, et al. Interleukin-6 delays neutrophil apoptosis. Arch Surg 1996; 131: 24–9CrossRefGoogle Scholar
  166. 166.
    Johnson ML, Billiar TR. The role of nitric oxide in surgical infection and sepsis. World J Surg 1998; 22: 187–96PubMedCrossRefGoogle Scholar
  167. 167.
    Cetinkale O, Belce A, Konukoglu D, et al. Evaluation of lipid peroxidation and total antioxidant status in plasma of rats following thermal injury. Burns 1997; 23: 114–6PubMedCrossRefGoogle Scholar
  168. 168.
    Sparkes BG. Influence of burn induced lipid-protein complex on IL-2 secretion by PBMC in vitro. Burns 1991; 17: 128–35PubMedCrossRefGoogle Scholar
  169. 169.
    Battal MN, Hata Y, Matsuka K, et al. Reduction of progressive burn injury by using a new non-selective endothelin-A and endothelin-B receptor antagonist. Plast Recon Surg 1997; 99: 1610–9CrossRefGoogle Scholar
  170. 170.
    Maxwell SR, Lip GR. Reperfusion injury: a review of the pathophysiology, clinical manifestations and therapeutic options. Int J Cardiol 1997; 58: 91–117CrossRefGoogle Scholar
  171. 171.
    Hack CE, Wolbink GJ, Schalkwijk C, et al. The role of secretory phospholipase A2 and C reactive protein in the removal of injured cells. Immunol Today 1997; 18: 111–5PubMedCrossRefGoogle Scholar
  172. 172.
    Hesselink MKC, Kuipers H, Geurten P, et al. Structural muscle damage and muscle strength after incremental number of isometric and forced lengthening contractions. J Muscle Res Cell Motil 1996; 17: 335–41PubMedCrossRefGoogle Scholar
  173. 173.
    Newham DJ, Ghosh G. Muscle fatigue and pain after eccentric contractions at long and short lengths. Clin Sci 1988; 74: 55–62Google Scholar
  174. 174.
    MacIntyre DL, Reid WD, McKenzie DC. Delayed muscle soreness. Sports Med 1995; 20: 24–40PubMedCrossRefGoogle Scholar
  175. 175.
    Rock CL, Dechert RE, Khilnani R, et al. Carotenoids and antioxidant vitamins in patients after burn injury. J Burn Care Rehab 1997; 18 (3): 269–78CrossRefGoogle Scholar
  176. 176.
    Leaper DJ. Risk factors for surgical infection. J Hosp Infect 1995; 30 Suppl.: 127–39Google Scholar
  177. 177.
    Kawakami M, Kaneko N, Anada H, et al. Measurement of interleukin-6, interleukin-10, and tumor necrosis factor-alpha levels in tissues and plasma after thermal injury in mice. Surgery 1997; 121: 440–8PubMedCrossRefGoogle Scholar
  178. 178.
    Ohzato H, Monden M, Yoshizaki K. Systemic production of interleukin-6 following acute inflammation. Biochem Biophys Res Commun 1993; 197: 1556–62PubMedCrossRefGoogle Scholar
  179. 179.
    Yamada Y, Endo S, Inada K. Plasma cytokine levels in patients with severe burn injury — with reference to the relationship between infection and prognosis. Burns 1996; 22: 587–93PubMedCrossRefGoogle Scholar
  180. 180.
    O’Riordan DS, Mendez MV, O’Riordan MG. Molecular mechanisms of decreased IL-2 production after thermal injury. Surgery 1993; 114: 407–15Google Scholar
  181. 181.
    Schinkel C, Zimmer S, Kremer JP, et al. Comparative analysis of transcription and protein release of the inflammatory cytokines interleukin-1 beta (IL-1β) and interleukin-8 (IL-8) following major burn and mechanical trauma. Shock 1995; 4: 241–6PubMedCrossRefGoogle Scholar
  182. 182.
    Marano MA, Fong Y, Moldawer LL. Serum cachectin and tumor necrosis factor in critically ill patients with burns correlates with infection and mortality. Surg Gynecol Obstet 170: 32–8Google Scholar
  183. 183.
    Gadd MA, Hansbrough JF, Hoyt DA, et al. Defective T-cell surface antigen expression after mitogen stimulation. Ann Surg 1989; 20: 112–8CrossRefGoogle Scholar
  184. 184.
    Hariri RJ, Chang VA, Barie PS, et al. Traumatic injury induces interleukin-6 production by human astrocytes. Brain Res 1994; 636: 139–42PubMedCrossRefGoogle Scholar
  185. 185.
    Kleinschmidt S, Wanner GA, Bubmann D, et al. Proinflammatory cytokine gene expression in whole blood from patients undergoing coronary bypass surgery and its modulation by pentoxifylline. Shock 1998; 9: 12–20PubMedCrossRefGoogle Scholar
  186. 186.
    Martin C, Boisson C, Haccoun M, et al. Patterns of cytokine evolution (tumor necrosis factor and interleukin-6) after septic shock, hemorrhagic shock and severe trauma. Crit Care Med 1997; 25: 1813–9PubMedCrossRefGoogle Scholar
  187. 187.
    Pirenne J, Mahieu X, de Groote D, et al. Effect of cardiac surgery on cytokine production. Cytokine Res 1993; 43: 13–8Google Scholar
  188. 188.
    Ayala A, Lehmann DL, Herdon CD, et al. Mechanism of enhanced susceptibility to sepsis following hemorrhage: interleukin-10 suppression of T cell response is mediated by eicosanoid-induced interleukin-4 release. Arch Surg 1994; 129: 1172–8PubMedCrossRefGoogle Scholar
  189. 189.
    van der Poll T, Lowry SF. Tumor necrosis factor in sepsis: mediator of multiple organ failure of essential part of host response? Shock 1995; 3: 1–12PubMedGoogle Scholar
  190. 190.
    Michie HR, Manogue KR, Spriggs DR, et al. Detection of circulating tumor necrosis factor after endotoxin administration. N Engl J Med 1988; 318: 1481–6PubMedCrossRefGoogle Scholar
  191. 191.
    Pruitt JH, Copeland EMI, Moldawer LL. Interleukin-1 and Interleukin-1 antagonism in sepsis, systemic inflammatory response syndrome, and septic shock. Shock 1995; 3: 235–51PubMedCrossRefGoogle Scholar
  192. 192.
    Hesse DG, Tracey KJ, Fong Y, et al. Cytokine appearance in human endotoxemia and primate bacteremia. Surg Gynecol Obstet 1988; 166: 147–53PubMedGoogle Scholar
  193. 193.
    Levi M, van der Poll T, Cate H, et al. The cytokine-mediated imbalance between coagulant and anticoagulant mechanisms in sepsis and endotoxernia. Eur J Clin Invest 1997; 27: 3–9PubMedCrossRefGoogle Scholar
  194. 194.
    Fong Y, Tracey KJ, Moldawer LL, et al. Antibodies to cachectin/tumor necrosis factor reduce interleukin-1 beta and interleukin-6 appearance during lethal bacteremia. J Exp Med 1989; 170: 1627–33PubMedCrossRefGoogle Scholar
  195. 195.
    DuBose DA, Basamania K, Maglione L, et al. Role of bacterial endotoxins of intestinal origin in rat heat stress mortality. J Appl Physiol 1983; 54: 31–6PubMedGoogle Scholar
  196. 196.
    Rosenberg AT, Brock Utne JG, Gaffin SL, et al. Strenuous exercise causes systemic endotoxemia. J Appl Physiol 1988; 65: 106–8Google Scholar
  197. 197.
    Brock Utne JG, Gaffin SL, Wells MT, et al. Endotoxemia in exhausted runners after a long-distance race. S Aft Med J 1988; 73: 533–6Google Scholar
  198. 198.
    Stricter RM, Kunkel SL, Bone RC. Role of tumor necrosis factor-alpha in disease states and inflammation. Crit Care Med 1993; 21: S447–63CrossRefGoogle Scholar
  199. 199.
    Napolitano L, Campbell C, Bass BL. Kinetics of splenocyte interleukin-4 production after injury and lethal endotoxic challenge. J Surg Res 1997; 67: 33–9PubMedCrossRefGoogle Scholar
  200. 200.
    Scotte M, Masson S, Lyoumi S, et al. Cytokine gene expression in liver following minor or major hepatectomy in rat. Cytokine 1997; 9: 859–67PubMedCrossRefGoogle Scholar
  201. 201.
    Odeh M. Tumor necrosis factor-alpha as a myocardial depressant substance. Int J Cardiol 1993; 42: 231–8PubMedCrossRefGoogle Scholar
  202. 202.
    Cannon JG, Kluger MJ. Endogenous pyrogen activity in human plasma after exercise. Science 1983; 220: 617–9PubMedCrossRefGoogle Scholar
  203. 203.
    Ford R, Tamayo A, Martin B, et al. Identification of B -cell growth factors (interleukin 14; high molecular weight B-cell growth factors) in effusion fluids from patients with aggressive B-cell lymphomas. Blood 1995; 86: 283–93PubMedGoogle Scholar
  204. 204.
    Dent LA, Munro G, Piper KP, et al. Eosinophilic interleukin 5 (IL-5) transgenic mice: eosinophil activity and impaired clearance of Schistosoma mansoni. Parasite Immunol 1997; 19: 291–300PubMedCrossRefGoogle Scholar
  205. 205.
    Hirai K, Miyamasu M, Takaishi T, et al. Regulation of the function of eosinophils and basophils. Crit Rev Immunol 1997; 17: 325–52PubMedCrossRefGoogle Scholar
  206. 206.
    Gessner A, Blum H, Rollinghoff M. Differential regulation of IL-9 expression after infection with Leishmania major in susceptible and resistant mice. Immunobiology 1993; 189: 419–35PubMedCrossRefGoogle Scholar
  207. 207.
    Lim KG, Wan H-C, Bozza PT, et al. Human eosinophils elaborate the lymphocyte chemoattractants ILr16 (lymphocyte chemoattractant factor) and RANTES. J Immunol 1996; 156: 2566–70PubMedGoogle Scholar
  208. 208.
    Fossiez F, Djossou O, Chomarat P, et al. T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines. J Exp Med 1996; 183: 2593–603PubMedCrossRefGoogle Scholar
  209. 209.
    Stoll S, Muller G, Kurimoto M, et al. Production of IL-18 (IFN-gamma inducing factor) messenger RNA and functional protein by murine keratinocytes. J Immunol 1997; 159: 298–302PubMedGoogle Scholar
  210. 210.
    Yao Z, Painter SL, Fanslow WC, et al. Human IL-17: a novel cytokine derived from T cells. J Immunol 1995; 155: 5483–6PubMedGoogle Scholar
  211. 211.
    Kurzrock R, Estrov Z, Wetzler M, et al. LIF: not just a leukemia inhibitory factor. Endocrine Rev 1991; 12: 208–17CrossRefGoogle Scholar
  212. 212.
    Rohde T, Ostrowski K, Zacho M, et al. Evidence that IL-6 is produced in skeletal muscle during intense long-term muscle activity. Eur J Physiol 1998; 78: 448–53CrossRefGoogle Scholar
  213. 213.
    Fujisawa H, Shivji GM, Kondo H. Effect of a novel topical immunomodulatory, S-28463, on keratinocyte cytokine gene expression and production. J Interferon Res 1996; 16: 555–9CrossRefGoogle Scholar

Copyright information

© Adis International Limited 2001

Authors and Affiliations

  • Andrei I. Moldoveanu
    • 1
  • Roy J. Shephard
    • 1
    • 2
    • 3
    • 4
  • Pang N. Shek
    • 1
    • 2
    • 4
    • 5
  1. 1.Program in Exercise Sciences, Graduate Department of Community HealthUniversity of TorontoTorontoCanada
  2. 2.Faculty of Physical Education and HealthUniversity of TorontoTorontoCanada
  3. 3.Department of Public Health SciencesUniversity of TorontoTorontoCanada
  4. 4.Defence and Civil Institute of Environmental MedicineTorontoCanada
  5. 5.Department of Laboratory Medicine and PathobiologyUniversity of TorontoTorontoCanada

Personalised recommendations