1. Frohman EM. Multiple sclerosis. Med Clin North Am 2003; 87: 867–97, viii-x

2. White LJ, Castellano V. Exercise and brain health — implications for multiple sclerosis: part I — neuronal growth factors. Sports Med 2008; 38 (2): 91–100

3. Kempermann G, van Praag H, Gage FH. Activity—dependent regulation of neuronal plasticity and self repair. Prog Brain Res 2000; 127: 35–48

4. Edgerton VR, Roy RR. Paralysis recovery in humans and model systems. Curr Opin Neurobiol 2002; 12: 658–67

5. Edgerton VR, Tillakaratne NJ, Bigbee AJ, et al. Plasticity of the spinal neural circuitry after injury. Annu Rev Neurosci 2004; 27: 145–67

6. Febbraio MA, Pedersen BK. Muscle—derived interleukin−6: mechanisms for activation and possible biological roles. Faseb J 2002; 16: 1335–47

7. Pedersen BK, Steensberg A, Fischer C, et al. Searching for the exercise factor: is IL−6 a candidate? J Muscle Res Cell Motil 2003; 24: 113–9

8. Pedersen BK, Steensberg A, Schjerling P, et al. Exercise and interleukin−6. Curr Opin Hematol 2001; 8: 137–41

9. Kerschensteiner M, Stadelmann C, Dechant G, et al. Neurotrophic cross—talk between the nervous and immune systems: implications for neurological diseases. Ann Neurol 2003; 53: 292–304

10. Oppenheim JJ. Cytokines: past, present, and future. Int J Hematol 2001; 74: 3–8

11. Ozenci V, Kouwenhoven M, Link H. Cytokines in multiple sclerosis: methodological aspects and pathogenic implications. Mult Scler 2002; 8: 396–404

12. Persidsky Y. Model systems for studies of leukocyte migration across the blood—brain barrier. J Neurovirol 1999; 5: 579–90

13. Elenkov IJ, Chrousos GP. Stress hormones, proinflammatory and antiinflammatory cytokines, and autoimmunity. Ann N Y Acad Sci 2002; 966: 290–303

14. van Boxel-Dezaire AH, Hoff SC, et al. Decreased interleukin−10 and increased interleukin−12p40 mRNA are associated with disease activity and characterize different disease stages in multiple sclerosis. Ann Neurol 1999; 45: 695–703

15. Brosnan CF, Raine CS. Mechanisms of immune injury in multiple sclerosis. Brain Pathol 1996; 6: 243–57

16. Moreau T, Coles A, Wing M, et al. Transient increase in symptoms associated with cytokine release in patients with multiple sclerosis. Brain 1996; 119 (Pt 1): 225–37

17. Raine CS. Multiple sclerosis: TNF revisited, with promise. Nat Med 1995; 1: 211–4

18. Selmaj K, Brosnan CF, Raine CS. Expression of heat shock protein−65 by oligodendrocytes in vivo and in vitro: implications for multiple sclerosis. Neurology 1992; 42: 795–800

19. Steinman L. Escape from “horror autotoxicus”: pathogenesis and treatment of autoimmune disease. Cell 1995; 80: 7–10

20. Martiney JA, Cuff C, Litwak M, et al. Cytokine—induced inflammation in the central nervous system revisited. Neurochem Res 1998; 23: 349–59

21. Hartung HP, Reiners K, Archelos JJ, et al. Circulating adhesion molecules and tumor necrosis factor receptor in multiple sclerosis: correlation with magnetic resonance imaging. Ann Neurol 1995; 38: 186–93

22. Selmaj KW, Raine CS. Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro. Ann Neurol 1988; 23: 339–46

23. Feuerstein GZ, Liu T, Barone FC. Cytokines, inflammation, and brain injury: role of tumor necrosis factor—alpha. Cerebrovasc Brain Metab Rev 1994; 6: 341–60

24. Zimmerman GA, Weingarten K, Lavyne MH. Symptomatic lumbar epidural varices: report of two cases. J Neurosurg 1994; 80: 914–8

25. Ozenci V, Kouwenhoven M, Huang YM, et al. Multiple sclerosis is associated with an imbalance between tumour necrosis factor—alpha (TNF—alpha)— and IL−10−secreting blood cells that is corrected by interferon—beta (IFN—beta) treatment. Clin Exp Immunol 2000; 120: 147–53

26. Schwid SR, Thornton CA, Pandya S, et al. Quantitative assessment of motor fatigue and strength in MS. Neurology 1999; 53: 743–50

27. Spector NH. Neuroimmunomodulation: a brief review. Can conditioning of natural killer cell activity reverse cancer and/or aging? Regul Toxicol Pharmacol 1996; 24: S32–8

28. Stuve O, Cree BC, von Budingen HC, et al. Approved and future pharmacotherapy for multiple sclerosis. Neurologist 2002; 8: 290–301

29. Beebe AM, Cua DJ, de Waal Malefyt R. The role of interleukin−10 in autoimmune disease: systemic lupus erythematosus (SLE) and multiple sclerosis (MS). Cytokine Growth Factor Rev 2002; 13: 403–12

30. Kennedy MK, Torrance DS, Picha KS, et al. Analysis of cytokine mRNA expression in the central nervous system of mice with experimental autoimmune encephalomyelitis reveals that IL−10 mRNA expression correlates with recovery. J Immunol 1992; 149: 2496–505

31. Balashov KE, Comabella M, Ohashi T, et al. Defective regulation of IFNgamma and IL−12 by endogenous IL−10 in progressive MS. Neurology 2000; 55: 192–8

32. Navikas V, Link H. Review: cytokines and the pathogenesis of multiple sclerosis. J Neurosci Res 1996; 45: 322–33

33. Ellison MD, Merchant RE. Appearance of cytokine—associated central nervous system myelin damage coincides temporally with serum tumor necrosis factor induction after recombinant interleukin−2 infusion in rats. J Neuroimmunol 1991; 33: 245–51

34. Heesen C, Gold SM, Hartmann S, et al. Endocrine and cytokine responses to standardized physical stress in multiple sclerosis. Brain Behav Immun 2003; 17: 473–81

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

36. Shepard RJ, Shek PN. Impact of physical activity and sport on the immune system. Rev Environ Health 1996; 11: 133–47

37. Moldoveanu AI, Shephard RJ, Shek PN. The cytokine response to physical activity and training. Sports Med 2001; 31 (2): 115–44

38. Smith JK, Dykes R, Douglas JE, et al. Long—term exercise and atherogenic activity of blood mononuclear cells in persons at risk of developing ischemic heart disease. JAMA 1999; 281: 1722–7

39. Castaneda C, Gordon PL, Parker RC, et al. Resistance training to reduce the malnutrition—inflammation complex syndrome of chronic kidney disease. Am J Kidney Dis 2004; 43: 607–16

40. Goldhammer E, Tanchilevitch A, Maor I, et al. Exercise training modulates cytokines activity in coronary heart disease patients. Int J Cardiol 2005; 100: 93–9

41. Petitto JM, Streit WJ, Huang Z, et al. Interleukin−2 gene deletion produces a robust reduction in susceptibility to experimental autoimmune encephalomyelitis in C57BL/6 mice. Neurosci Lett 2000; 285: 66–70

42. 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: 188–95

43. White L, Castellano V, Mc Coy S. Cytokine changes after a resistance training program in multiple sclerosis patients. J Sport Sci 2006; 24: 1–4

44. Le Page C, Ferry A, Rieu M. Effect of muscular exercise on chronic relapsing experimental autoimmune encephalomyelitis. J Appl Physiol 1994; 77: 2341–7

45. Schulz KH, Gold SM, Witte J, et al. Impact of aerobic training on immune—endocrine parameters, neurotrophic factors, quality of life and coordinative function in multiple sclerosis. J Neurol Sci 2004; 225: 11–8

46. Elfont R. Emerging therapies. In: Burks J, editor. Multiple sclerosis. New York: Demos Medical Publishing, 2000: 193

47. Noronha A, Toscas A, Jensen MA. Interferon beta decreases T cell activation and interferon gamma production in multiple sclerosis. J Neuroimmunol 1993; 46: 145–53

48. 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

49. Pedersen BK, Steensberg A, Fischer C, et al. The metabolic role of IL−6 produced during exercise: is IL−6 an exercise factor? Proc Nutr Soc 2004; 63: 263–7

50. Pedersen BK, Akerström TC, Nielsen AR, et al. Role of myokines in exercise and metabolism. J Appl Physiol 2007; 103 (3): 1093–8

51. Sheppard RJ. Exercise and cytokines. In: Mackinnon LT, editor. Advances in exercise immunology. Champaign (IL): Human Kinetics, 1999: 364

52. Plomgaard P, Penkowa M, Pedersen BK. Fiber type specific expression of TNF—alpha, IL−6 and IL−18 in human skeletal muscles. Exerc Immunol Rev 2005; 11: 53–63

53. Cannon JG, Meydani SN, Fielding RA, et al. Acute phase response in exercise: II. Associations between vitamin E, cytokines, and muscle proteolysis. Am J Physiol 1991; 260: R1235–40

54. Dufaux B, Order U. Complement activation after prolonged exercise. Clin Chim Acta 1989; 179: 45–9

55. Drenth JP, Van Uum SH, Van Deuren M, et al. Endurance run increases circulating IL−6 and IL−1ra but downregulates ex vivo TNF—alpha and IL−1 beta production. J Appl Physiol 1995; 79: 1497–503

56. Smith JA, Telford RD, Baker MS, et al. Cytokine immunoreactivity in plasma does not change after moderate endurance exercise. J Appl Physiol 1992; 73: 1396–401

57. Mellor AL, Munn D, Chandler P, et al. Tryptophan catabolism and T cell responses. Adv Exp Med Biol 2003; 527: 27–35

58. Pahan K, Smith BT, Singh AK, et al. Cytochrome P−450 2E1 in rat liver peroxisomes: downregulation by ischemia/reperfusion—induced oxidative stress. Free Radic Biol Med 1997; 23: 963–71

59. Stanislaus R, Pahan K, Singh AK, et al. Amelioration of experimental allergic encephalomyelitis in Lewis rats by lovastatin. Neurosci Lett 1999; 269: 71–4

60. Okazaki H, Nagashima T, Minota S. Immunomodulatory activities of statins [in Japanese]. Nihon Rinsho Meneki Gakkai Kaishi 2004; 27: 357–60

61. Vollmer T, Key L, Durkalski V, et al. Oral simvastatin treatment in relapsing—remitting multiple sclerosis. Lancet 2004; 363: 1607–8

62. Desvergne B, Wahli W. Peroxisome proliferator—activated receptors: nuclear control of metabolism. Endocr Rev 1999; 20: 649–88

63. Constantinescu CS, Grossman RI, Finelli PF, et al. Clinical and subclinical neurological involvement in children of conjugal multiple sclerosis patients. Mult Scler 1995; 1: 170–2

64. Lovett-Racke AE, Hussain RZ, Northrop S, et al. Peroxisome proliferator—activated receptor alpha agonists as therapy for autoimmune disease. J Immunol 2004; 172: 5790–8

65. Ehrhard PB, Erb P, Graumann U, et al. Expression of nerve growth factor and nerve growth factor receptor tyrosine kinase Trk in activated CD4−positive T—cell clones. Proc Natl Acad Sci U S A 1993; 90: 10984–8

66. Leon A, Buriani A, Dal Toso R, et al. Mast cells synthesize, store, and release nerve growth factor. Proc Natl Acad Sci U S A 1994; 91: 3739–43

67. Santambrogio L, Benedetti M, Chao MV, et al. Nerve growth factor production by lymphocytes. J Immunol 1994; 153: 4488–95

68. Besser M, Wank R. Cutting edge: clonally restricted production of the neurotrophins brain—derived neurotrophic factor and neurotrophin−3 mRNA by human immune cells and Th1/Th2−polarized expression of their receptors. J Immunol 1999; 162: 6303–6

69. Braun A, Lommatzsch M, Lewin GR, et al. Neurotrophins: a link between airway inflammation and airway smooth muscle contractility in asthma? Int Arch Allergy Immunol 1999; 118: 163–5

70. Moalem G, Gdalyahu A, Shani Y, et al. Production of neurotrophins by activated T cells: implications for neuroprotective autoimmunity. J Autoimmun 2000; 15: 331–45

71. Villoslada P, Hauser SL, Bartke I, et al. Human nerve growth factor protects common marmosets against autoimmune encephalomyelitis by switching the balance of T helper cell type 1 and 2 cytokines within the central nervous system. J Exp Med 2000; 191: 1799–806

72. Micera A, Properzi F, Triaca V, et al. Nerve growth factor antibody exacerbates neuropathological signs of experimental allergic encephalomyelitis in adult Lewis rats. J Neuroimmunol 2000; 104: 116–23

73. Steinman L. Engineering better cytokines. Nat Biotechnol 2003; 21: 1293–4

74. Elenkov IJ, Chrousos GP, Wilder RL. Neuroendocrine regulation of IL−12 and TNF—alpha/IL−10 balance: clinical implications. Ann N Y Acad Sci 2000; 917: 94–105

75. Webster JI, Tonelli L, Sternberg EM. Neuroendocrine regulation of immunity. Annu Rev Immunol 2002; 20: 125–63

76. Goodin DS, Ebers GC, Johnson KP, et al. The relationship of MS to physical trauma and psychological stress: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 1999; 52: 1737–45

77. Martinelli V. Trauma, stress and multiple sclerosis. Neurol Sci 2000; 21: S849–52

78. Bukilica M, Djordjevic S, Maric I, et al. Stress—induced suppression of experimental allergic encephalomyelitis in the rat. Int J Neurosci 1991; 59: 167–75

79. Griffin AC, Lo WD, Wolny AC, et al. Suppression of experimental autoimmune encephalomyelitis by restraint stress: sex differences. J Neuroimmunol 1993; 44: 103–16

80. Levine S, Wenk EJ. Hyperacute allergic encephalomyelitis: lymphatic system as site of adjuvant effect of pertussis vaccine. Am J Pathol 1967; 50: 465–83

81. Levine S, Sowinski R. The role of the adrenal in relapses of experimental allergic encephalomyelitis. Proc Soc Exp Biol Med 1975; 149: 1032–5

82. Levine S, Saltzman A. Nonspecific stress prevents relapses of experimental allergic encephalomyelitis in rats. Brain Behav Immun 1987; 1: 336–41

83. Elenkov IJ. Systemic stress—induced Th2 shift and its clinical implications. Int Rev Neurobiol 2002; 52: 163–86

84. Schumann EM, Kumpfel T, Then Bergh F, et al. Activity of the hypothalamic—pituitary—adrenal axis in multiple sclerosis: correlations with gadolinium—enhancing lesions and ventricular volume. Ann Neurol 2002; 51: 763–7

85. Besedovsky HO, del Rey A. Immune—neuro—endocrine interactions: facts and hypotheses. Endocr Rev 1996; 17: 64–102

86. Luger A, Deuster PA, Kyle SB, et al. Acute hypothalamicpituitary—adrenal responses to the stress of treadmill exercise: physiologic adaptations to physical training. N Engl J Med 1987; 316: 1309–15

87. Hasko G, Szabo C, Nemeth ZH, et al. Stimulation of beta—adrenoceptors inhibits endotoxin—induced IL−12 production in normal and IL−10 deficient mice. J Neuroimmunol 1998; 88: 57–61

88. Panina-Bordignon P, Mazzeo D, Lucia PD, et al. Beta2−agonists prevent Th1 development by selective inhibition of interleukin 12. J Clin Invest 1997; 100: 1513–9

89. Oleshansky MA, Zoltick JM, Herman RH, et al. The influence of fitness on neuroendocrine responses to exhaustive treadmill exercise. Eur J Appl Physiol Occup Physiol 1990; 59: 405–10