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

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Sports Medicine
Published in: Sports Medicine 3/2008

01-03-2008 | Leading Article

Exercise and Brain Health — Implications for Multiple Sclerosis

Part II — Immune Factors and Stress Hormones

Authors: Dr Lesley J. White, Vanessa Castellano

Published in: Sports Medicine | Issue 3/2008

Login to get access

Abstract

Part I of this review addressed the possible modulatory role of exercise on neuronal growth factors to promote brain health in neurodegenerative diseases such as multiple sclerosis (MS), which is characterized by varied patterns of inflammation, demyelination and axonal loss. Part II presents evidence that supports the potential neuroprotective effect of exercise on the modulation of immune factors and stress hormones in MS. Many current therapies used to attenuate MS progression are mediated, at least in part, through alterations in the relative concentrations of pro- and anti-inflammatory cytokines. Exercise-induced alterations in local and systemic cytokine production may also benefit immune function in health and disease. Exercise immunomodulation appears to be mediated by a complex interaction of hormones, cytokines and neural factors that may favorably influence immune variables in MS. The promising interplay between exercise and brain health in MS deserves further investigation.
Literature
1.
2.
White LJ, Castellano V. Exercise and brain health — implications for multiple sclerosis: part I — neuronal growth factors. Sports Med 2008; 38 (2): 91–100PubMedCrossRef
3.
Kempermann G, van Praag H, Gage FH. Activity—dependent regulation of neuronal plasticity and self repair. Prog Brain Res 2000; 127: 35–48PubMedCrossRef
4.
Edgerton VR, Roy RR. Paralysis recovery in humans and model systems. Curr Opin Neurobiol 2002; 12: 658–67PubMedCrossRef
5.
Edgerton VR, Tillakaratne NJ, Bigbee AJ, et al. Plasticity of the spinal neural circuitry after injury. Annu Rev Neurosci 2004; 27: 145–67PubMedCrossRef
6.
Febbraio MA, Pedersen BK. Muscle—derived interleukin−6: mechanisms for activation and possible biological roles. Faseb J 2002; 16: 1335–47PubMedCrossRef
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: 113–9PubMedCrossRef
8.
Pedersen BK, Steensberg A, Schjerling P, et al. Exercise and interleukin−6. Curr Opin Hematol 2001; 8: 137–41PubMedCrossRef
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: 292–304PubMedCrossRef
10.
11.
Ozenci V, Kouwenhoven M, Link H. Cytokines in multiple sclerosis: methodological aspects and pathogenic implications. Mult Scler 2002; 8: 396–404PubMedCrossRef
12.
Persidsky Y. Model systems for studies of leukocyte migration across the blood—brain barrier. J Neurovirol 1999; 5: 579–90PubMedCrossRef
13.
Elenkov IJ, Chrousos GP. Stress hormones, proinflammatory and antiinflammatory cytokines, and autoimmunity. Ann N Y Acad Sci 2002; 966: 290–303PubMedCrossRef
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: 695–703PubMedCrossRef
15.
Brosnan CF, Raine CS. Mechanisms of immune injury in multiple sclerosis. Brain Pathol 1996; 6: 243–57PubMedCrossRef
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): 225–37PubMedCrossRef
17.
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: 795–800PubMedCrossRef
19.
Steinman L. Escape from “horror autotoxicus”: pathogenesis and treatment of autoimmune disease. Cell 1995; 80: 7–10PubMedCrossRef
20.
Martiney JA, Cuff C, Litwak M, et al. Cytokine—induced inflammation in the central nervous system revisited. Neurochem Res 1998; 23: 349–59PubMedCrossRef
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: 186–93PubMedCrossRef
22.
Selmaj KW, Raine CS. Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro. Ann Neurol 1988; 23: 339–46PubMedCrossRef
23.
Feuerstein GZ, Liu T, Barone FC. Cytokines, inflammation, and brain injury: role of tumor necrosis factor—alpha. Cerebrovasc Brain Metab Rev 1994; 6: 341–60PubMed
24.
Zimmerman GA, Weingarten K, Lavyne MH. Symptomatic lumbar epidural varices: report of two cases. J Neurosurg 1994; 80: 914–8PubMedCrossRef
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: 147–53PubMedCrossRef
26.
Schwid SR, Thornton CA, Pandya S, et al. Quantitative assessment of motor fatigue and strength in MS. Neurology 1999; 53: 743–50PubMedCrossRef
27.
Spector NH. Neuroimmunomodulation: a brief review. Can conditioning of natural killer cell activity reverse cancer and/or aging? Regul Toxicol Pharmacol 1996; 24: S32–8CrossRef
28.
Stuve O, Cree BC, von Budingen HC, et al. Approved and future pharmacotherapy for multiple sclerosis. Neurologist 2002; 8: 290–301PubMedCrossRef
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: 403–12PubMedCrossRef
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: 2496–505PubMed
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: 192–8PubMedCrossRef
32.
Navikas V, Link H. Review: cytokines and the pathogenesis of multiple sclerosis. J Neurosci Res 1996; 45: 322–33PubMedCrossRef
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: 245–51PubMedCrossRef
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: 473–81PubMedCrossRef
35.
Nieman DC. Current perspective on exercise immunology. Curr Sports Med Rep 2003; 2: 239–42PubMed
36.
Shepard RJ, Shek PN. Impact of physical activity and sport on the immune system. Rev Environ Health 1996; 11: 133–47PubMed
37.
Moldoveanu AI, Shephard RJ, Shek PN. The cytokine response to physical activity and training. Sports Med 2001; 31 (2): 115–44PubMedCrossRef
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: 1722–7PubMedCrossRef
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: 607–16PubMedCrossRef
40.
Goldhammer E, Tanchilevitch A, Maor I, et al. Exercise training modulates cytokines activity in coronary heart disease patients. Int J Cardiol 2005; 100: 93–9PubMedCrossRef
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: 66–70PubMedCrossRef
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: 188–95PubMedCrossRef
43.
White L, Castellano V, Mc Coy S. Cytokine changes after a resistance training program in multiple sclerosis patients. J Sport Sci 2006; 24: 1–4CrossRef
44.
Le Page C, Ferry A, Rieu M. Effect of muscular exercise on chronic relapsing experimental autoimmune encephalomyelitis. J Appl Physiol 1994; 77: 2341–7PubMed
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: 11–8PubMedCrossRef
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: 145–53PubMedCrossRef
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: 371–6PubMedCrossRef
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: 263–7PubMedCrossRef
50.
Pedersen BK, Akerström TC, Nielsen AR, et al. Role of myokines in exercise and metabolism. J Appl Physiol 2007; 103 (3): 1093–8PubMedCrossRef
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: 53–63PubMed
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: 45–9PubMedCrossRef
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: 1497–503PubMed
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: 1396–401PubMed
57.
Mellor AL, Munn D, Chandler P, et al. Tryptophan catabolism and T cell responses. Adv Exp Med Biol 2003; 527: 27–35PubMedCrossRef
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: 963–71PubMedCrossRef
59.
Stanislaus R, Pahan K, Singh AK, et al. Amelioration of experimental allergic encephalomyelitis in Lewis rats by lovastatin. Neurosci Lett 1999; 269: 71–4PubMedCrossRef
60.
Okazaki H, Nagashima T, Minota S. Immunomodulatory activities of statins [in Japanese]. Nihon Rinsho Meneki Gakkai Kaishi 2004; 27: 357–60PubMedCrossRef
61.
Vollmer T, Key L, Durkalski V, et al. Oral simvastatin treatment in relapsing—remitting multiple sclerosis. Lancet 2004; 363: 1607–8PubMedCrossRef
62.
Desvergne B, Wahli W. Peroxisome proliferator—activated receptors: nuclear control of metabolism. Endocr Rev 1999; 20: 649–88PubMedCrossRef
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: 170–2PubMed
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: 5790–8PubMed
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: 10984–8PubMedCrossRef
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: 3739–43PubMedCrossRef
67.
Santambrogio L, Benedetti M, Chao MV, et al. Nerve growth factor production by lymphocytes. J Immunol 1994; 153: 4488–95PubMed
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: 6303–6PubMed
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: 163–5PubMedCrossRef
70.
Moalem G, Gdalyahu A, Shani Y, et al. Production of neurotrophins by activated T cells: implications for neuroprotective autoimmunity. J Autoimmun 2000; 15: 331–45PubMedCrossRef
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: 1799–806PubMedCrossRef
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: 116–23PubMedCrossRef
73.
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: 94–105PubMedCrossRef
75.
Webster JI, Tonelli L, Sternberg EM. Neuroendocrine regulation of immunity. Annu Rev Immunol 2002; 20: 125–63PubMedCrossRef
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: 1737–45PubMedCrossRef
77.
Martinelli V. Trauma, stress and multiple sclerosis. Neurol Sci 2000; 21: S849–52CrossRef
78.
Bukilica M, Djordjevic S, Maric I, et al. Stress—induced suppression of experimental allergic encephalomyelitis in the rat. Int J Neurosci 1991; 59: 167–75PubMedCrossRef
79.
Griffin AC, Lo WD, Wolny AC, et al. Suppression of experimental autoimmune encephalomyelitis by restraint stress: sex differences. J Neuroimmunol 1993; 44: 103–16PubMedCrossRef
80.
Levine S, Wenk EJ. Hyperacute allergic encephalomyelitis: lymphatic system as site of adjuvant effect of pertussis vaccine. Am J Pathol 1967; 50: 465–83PubMed
81.
Levine S, Sowinski R. The role of the adrenal in relapses of experimental allergic encephalomyelitis. Proc Soc Exp Biol Med 1975; 149: 1032–5PubMed
82.
Levine S, Saltzman A. Nonspecific stress prevents relapses of experimental allergic encephalomyelitis in rats. Brain Behav Immun 1987; 1: 336–41PubMedCrossRef
83.
Elenkov IJ. Systemic stress—induced Th2 shift and its clinical implications. Int Rev Neurobiol 2002; 52: 163–86PubMedCrossRef
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: 763–7PubMedCrossRef
85.
Besedovsky HO, del Rey A. Immune—neuro—endocrine interactions: facts and hypotheses. Endocr Rev 1996; 17: 64–102PubMed
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: 1309–15PubMedCrossRef
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: 57–61PubMedCrossRef
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: 1513–9PubMedCrossRef
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: 405–10PubMedCrossRef
90.
Smith GD, Watson LP, Mathias CJ. Cardiovascular and catecholamine changes induced by supine exercise and upright posture in vasovagal syncope: comparisons with normal subjects and subjects with sympathetic denervation. Eur Heart J 1996; 17: 1882–90PubMedCrossRef
Metadata
Title
Exercise and Brain Health — Implications for Multiple Sclerosis
Part II — Immune Factors and Stress Hormones
Authors
Dr Lesley J. White
Vanessa Castellano
Publication date
01-03-2008
Publisher
Springer International Publishing
Published in
Sports Medicine / Issue 3/2008
Print ISSN: 0112-1642
Electronic ISSN: 1179-2035
DOI
https://doi.org/10.2165/00007256-200838030-00001

Other articles of this Issue 3/2008

Sports Medicine 3/2008 Go to the issue

Review Article

An Applied Research Model for the Sport Sciences

Review Article

Reticulocytes in Sports Medicine

Review Article

Fat and Carbohydrate Metabolism during Submaximal Exercise in Children

Review Article

Describing and Understanding Pacing Strategies during Athletic Competition