Journal Mobile Options
Table of Contents
Vol. 13, No. 5-6, 2006
Issue release date: August 2007
Section title: Paper
Neuroimmunomodulation 2006;13:318–326
(DOI:10.1159/000104860)

Stress and Disease Progression in Multiple Sclerosis and Its Animal Models

Gold S.M. · Heesen C.
aMultiple Sclerosis Program, Department of Neurology and Cousins Center for Psychoneuroimmunology, UCLA School of Medicine, Los Angeles, Calif., USA; bDepartment of Neurology, University Hospital Hamburg-Eppendorf, Hamburg, Germany

Do you have an account?

Register and profit from personalized services (MyKarger) Login Information

Please create your User ID & Password





Contact Information









I have read the Karger Terms and Conditions and agree.

Register and profit from personalized services (MyKarger) Login Information

Please create your User ID & Password





Contact Information









I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in

Buy

  • FullText & PDF
  • Unlimited re-access via MyKarger (new!)
  • Unrestricted printing, no saving restrictions for personal use
  • Reduced rates with a PPV account
read more

Direct: USD 38.00
Account: USD 26.50

Select

Rent/Cloud

  • Rent for 48h to view
  • Buy Cloud Access for unlimited viewing via different devices
  • Synchronizing in the ReadCube Cloud
  • Printing and saving restriction apply

Rental: USD 8.50
Cloud: USD 20.00

Select

Subscribe

  • Automatic perpetual access to all articles of the subscribed year(s)
  • Unlimited re-access via Subscriber Login or MyKarger
  • Unrestricted printing, no saving restrictions for personal use
read more

Subcription rates


Select


Article / Publication Details

First-Page Preview
Abstract of Paper

Received: 1/26/2007
Accepted: 3/10/2007
Published online: 8/22/2007

Number of Print Pages: 9
Number of Figures: 1
Number of Tables: 1

ISSN: 1021-7401 (Print)
eISSN: 1423-0216 (Online)

For additional information: http://www.karger.com/NIM

Abstract

Since the first description of multiple sclerosis (MS) by Charcot, stress has been hypothesized to be a potential trigger of relapses. In recent years, data from observational studies in MS patients have provided some support for an association between stress and MS relapses. Furthermore, studies employing the MS animal model experimental autoimmune encephalomyelitis have shown that certain stressors can exacerbate the disease if administered prior to disease induction. Several lines of research have explored the 2 major stress response systems – the hypothalamic-pituitary-adrenal axis and the autonomic nervous system – and their relation to disease course in MS and experimental autoimmune encephalomyelitis. These studies provide evidence that insensitivity of the immune system to signals from these systems may play a role in inflammatory events. These findings can be integrated into a biological model of stress response system alterations in MS.


Article / Publication Details

First-Page Preview
Abstract of Paper

Received: 1/26/2007
Accepted: 3/10/2007
Published online: 8/22/2007

Number of Print Pages: 9
Number of Figures: 1
Number of Tables: 1

ISSN: 1021-7401 (Print)
eISSN: 1423-0216 (Online)

For additional information: http://www.karger.com/NIM


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Charcot JM: Lectures on Diseases of the Nervous System. London, New Sydenham Society, 1877.
  2. Hemmer B, Archelos JJ, Hartung HP: New concepts in the immunopathogenesis of multiple sclerosis. Nat Rev Neurosci 2002;3:291–301.
  3. Sospedra M, Martin R: Immunology of multiple sclerosis. Annu Rev Immunol 2005;23:683–747.
  4. Lassmann H, Bruck W, Lucchinetti C: Heterogeneity of multiple sclerosis pathogenesis: implications for diagnosis and therapy. Trends Mol Med 2001;7:115–121.
  5. Evangelou N, Esiri MM, Smith S, Palace J, Matthews PM: Quantitative pathological evidence for axonal loss in normal appearing white matter in multiple sclerosis. Ann Neurol 2000;47:391–395.
  6. Confavreux C, Vukusic S: Accumulation of irreversible disability in multiple sclerosis: from epidemiology to treatment. Clin Neurol Neurosurg 2006;108:327–332.
  7. Confavreux C, Vukusic S, Adeleine P: Early clinical predictors and progression of irreversible disability in multiple sclerosis: an amnesic process. Brain 2003;126:770–782.
  8. Steinman L, Zamvil SS: Virtues and pitfalls of EAE for the development of therapies for multiple sclerosis. Trends Immunol 2005;26:565–571.
  9. Friese MA, Montalban X, Willcox N, Bell JI, Martin R, Fugger L: The value of animal models for drug development in multiple sclerosis. Brain 2006;129:1940–1952.
  10. Levine S, Strebel R, Wenk E, Harman P: Suppression of experimental autoimmune encephalomyelitis by stress. Exp Biol Med 1962;109:294–298.
  11. Levine S, Saltzman A: Nonspecific stress prevents relapses of experimental allergic encephalomyelitis in rats. Brain Behav Immun 1987;1:336–341.
  12. Whitacre CC, Dowdell K, Griffin AC: Neuroendocrine influences on experimental autoimmune encephalomyelitis. Ann NY Acad Sci 1998;840:705–716.
  13. Correa SG, Rodriguez-Galâan MC, Rivero VE, Riera CM: Chronic varied stress modulates experimental autoimmune encephalomyelitis in Wistar rats. Brain Behav Immun 1988;12:134–148.
  14. Kuroda Y, Mori T, Hori T: Restraint stress suppresses experimental allergic encephalomyelitis in Lewis rats. Brain Res Bull 1994;34:15–17.
  15. Campbell T, Meagher MW, Sieve A, Scott B, Storts R, Welsh TH, Welsh CJ: The effects of restraint stress on the neuropathogenesis of Theiler’s virus infection. 1. Acute disease. Brain Behav Immun 2001;15:235–254.
  16. Teunis MA, Heijnen CJ, Sluyter F, Bakker JM, Van Dam AM, Hof M, Cools AR, Kavelaars A: Maternal deprivation of rat pups increases clinical symptoms of experimental autoimmune encephalomyelitis at adult age. J Neuroimmunol 2002;133:30–38.
  17. Chandler N, Jacobson S, Esposito P, Connolly R, Theoharides TC: Acute stress shortens the time to onset of experimental allergic encephalomyelitis in SJL/J mice. Brain Behav Immun 2002;16:757–763.
  18. Le Page C, Bourdoulous S, Beraud E, Couraud PO, Rieu M, Ferry A: Effect of physical exercise on adoptive experimental auto-immune encephalomyelitis in rats. Eur J Appl Physiol Occup Physiol 1996;73:130–135.
  19. Goodin DS, Ebers GC, Johnson KP, Rodriguez M, Sibley WA, Wolinsky JS: 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;52:1737–1745.
  20. Mohr DC, Goodkin DE, Bacchetti P, Boudewyn AC, Huang L, Marietta P, Cheuk W, Dee B: Psychological stress and the subsequent appearance of new brain MRI lesions in MS. Neurology 2000;55:55–61.
  21. Ackerman KD, Stover A, Heyman R, Anderson BP, Houck PR, Frank E, Rabin BS, Baum A: Relationship between cardiovascular reactivity, stressful life events, and multiple sclerosis disease activity. Brain Behav Immun 2003;17:141–151.
  22. Buljevac D, Hop WC, Reedeker W, Janssens AC, van der Meche FG, van Doorn PA, Hintzen RQ: Self reported stressful life events and exacerbations in multiple sclerosis: prospective study. BMJ 2003;327:646.
  23. Mohr DC, Hart SL, Julian L, Cox D, Pelletier D: Association between stressful life events and exacerbation in multiple sclerosis: a meta-analysis. BMJ 2004;328:731–735.
  24. Nisipeanu P, Korczyn AD: Psychological stress as risk factor for exacerbations in multiple sclerosis. Neurology 1993;43:1311–1312.
  25. Li J, Johansen C, Bronnum-Hansen H, Stenager E, Koch-Henriksen N, Olsen J: The risk of multiple sclerosis in bereaved parents: a nationwide cohort study in Denmark. Neurology 2004;62:726–729.
  26. Webster JI, Tonelli L, Sternberg EM: Neuroendocrine regulation of immunity. Annu Rev Immunol 2002;20:125–163.
  27. DeRijk RH, Eskandari F, Sternberg EM: Corticosteroid resistance in a subpopulation of multiple sclerosis patients as measured by ex vivo dexamethasone inhibition of LPS induced IL-6 production. J Neuroimmunol 2004;151:180–188.
  28. van Winsen LM, Muris DF, Polman CH, Dijkstra CD, van den Berg TK, Uitdehaag BM: Sensitivity to glucocorticoids is decreased in relapsing remitting multiple sclerosis. J Clin Endocrinol Metab 2005;90:734–740.
  29. Wei T, Lightman SL: The neuroendocrine axis in patients with multiple sclerosis. Brain 1997;120:1067–1076.
  30. Then Bergh F, Grasser A, Trenkwalder C, Backmund H, Holsboer F, Rupprecht R: Binding characteristics of the glucocorticoid receptor in peripheral blood lymphocytes in multiple sclerosis. J Neurol 1999;246:292–298.
  31. Heesen C, Gold SM, Fischer I, Von der Mark I, Reich C, Saager C, Kucinski T, Otte C, Schulz KH: Hypothalamo-pituitary-adrenal axis dysregulation in MS – clinical, MRI and immune correlates. 22nd ECTRIMS Meeting, Madrid, September 2006.
  32. Fassbender K, Schmidt R, Mössner R, Kischka U, Kühnen J, Schwartz A, Hennerici M: Mood disorders and dysfunction of the hypothalamic-pituitary-adrenal axis in multiple sclerosis: association with cerebral inflammation. Arch Neurol 1998;55:66–72.
  33. Stefferl A, Storch MK, Linington C, Stadelmann C, Lassmann H, Pohl T, Holsboer F, Tilders FJ, Reul JM: Disease progression in chronic relapsing experimental allergic encephalomyelitis is associated with reduced inflammation-driven production of corticosterone. Endocrinol 2001;142:3616–3624.
  34. Erkut ZA, Endert E, Huitinga I, Swaab DF: Cortisol is increased in postmortem cerebrospinal fluid of multiple sclerosis patients: relationship with cytokines and sepsis. Mult Scler 2002;8:229–236.
  35. Huitinga I, Erkut ZA, van Beurden D, Swaab DF: The hypothalamo-pituitary-adrenal axis in multiple sclerosis. Ann NY Acad Sci 2003;992:118–128.
  36. Tracey KJ: The inflammatory reflex. Nature 2002;420:853–859.
  37. Czura CJ, Tracey KJ: Autonomic neural regulation of immunity. J Intern Med 2005;257:156–166.
  38. Karaszewski JW, Reder AT, Maselli R, Brown M, Arnason BG: Sympathetic skin responses are decreased and lymphocyte β-adrenergic receptors are increased in progressive multiple sclerosis. Ann Neurol 1990;27:366–372.
  39. Zoukos Y, Leonard JP, Thomaides T, Thompson AJ, Cuzner ML: β-Adrenergic receptor density and function of peripheral blood mononuclear cells are increased in multiple sclerosis: a regulatory role for cortisol and interleukin-1. Ann Neurol 1992;31:657–662.
  40. Karaszewski JW, Reder AT, Anlar B, Kim WC, Arnason BG: Increased lymphocyte β-adrenergic receptor density in progressive multiple sclerosis is specific for the CD8+, CD28– suppressor cell. Ann Neurol 1991;30:42–47.
  41. Zoukos Y, Kidd D, Woodroofe MN, Kendall BE, Thompson AJ, Cuzner ML: Increased expression of high affinity IL-2 receptors and β-adrenoceptors on peripheral blood mononuclear cells is associated with clinical and MRI activity in multiple sclerosis. Brain 1994;117:307–315.
  42. Zoukos Y, Thomaides TN, Kidd D, Cuzner ML, Thompson A: Expression of β2 adrenoreceptors on peripheral blood mononuclear cells in patients with primary and secondary progressive multiple sclerosis: a longitudinal six month study. J Neurol Neurosurg Psychiatry 2003;74:197–202.
  43. Heesen C, Gold SM, Sondermann J, Tessmer W, Schulz KH: Oral terbutaline differentially affects cytokine (IL-10, IL-12, TNF, IFNg) release in multiple sclerosis patients and controls. J Neuroimmunol 2002;132:189–195.
  44. Haerter K, Vroon A, Kavelaars A, Heijnen CJ, Limmroth V, Espinosa E, Schedlowski M, Elsenbruch S: In vitro adrenergic modulation of cellular immune functions in experimental autoimmune encephalomyelitis. J Neuroimmunol 2004;146:126–132.
  45. Giorelli M, Livrea P, Trojano M: Post-receptorial mechanisms underlie functional dysregulation of β2-adrenergic receptors in lymphocytes from multiple sclerosis patients. J Neuroimmunol 2004;155:143–149.
  46. Vroon A, Kavelaars A, Limmroth V, Lombardi MS, Goebel MU, Van Dam AM, Caron MG, Schedlowski M, Heijnen CJ: G protein-coupled receptor kinase 2 in multiple sclerosis and experimental autoimmune encephalomyelitis. J Immunol 2005;174:4400–4406.
  47. Heesen C, Gold SM, Raji A, Wiedemann K, Schulz KH: Cognitive impairment correlates with hypothalamo-pituitary-adrenal axis dysregulation in multiple sclerosis. Psychoneuroendocrinology 2002;27:505–517.
  48. Then Bergh F, Kumpfel T, Trenkwalder C, Rupprecht R, Holsboer F: Dysregulation of the hypothalamo-pituitary-adrenal axis is related to the clinical course in multiple sclerosis. Neurology 1999;53:772–777.
  49. Schumann EM, Kumpfel T, Then Bergh F, Trenkwalder C, Holsboer F, Auer DP: Activity of the hypothalamic-pituitary-adrenal axis in multiple sclerosis: correlations with gadolinium-enhancing lesions and ventricular volume. Ann Neurol 2002;51:763–767.
  50. Gold SM, Mohr DC, Huitinga I, Flachenecker P, Sternberg EM, Heesen C: The role of stress-response systems for the pathogenesis and progression of multiple sclerosis. Trends Immunol 2005;26:644–651.
  51. Bjartmar C, Trapp BD: Axonal and neuronal degeneration in multiple sclerosis: mechanisms and functional consequences. Curr Opin Neurol 2001;14:271–288.
  52. Gold SM, Raji A, Huitinga I, Wiedemann K, Schulz KH, Heesen C: Hypothalamo-pituitary-adrenal axis activity predicts disease progression in multiple sclerosis. J Neuroimmunol 2005;165:186–191.
  53. De Keyser J, Wilczak N, Leta R, Streetland C: Astrocytes in MS lack β2-adrenergic receptors. Neurology 1999;53:1628–1633.
  54. De Keyser J, Zeinstra E, Wilczak N: Astrocytic β2-adrenergic receptors and multiple sclerosis. Neurobiol Dis 2004;15:331–339.
  55. Miller GE, Chen E: Life stress and diminished expression of genes encoding glucocorticoid receptor and β2-adrenergic receptor in children with asthma. Proc Natl Acad Sci USA 2006;103:5496–5501.
  56. Straub RH, Dhabhar FS, Bijlsma JWJ, Cutolo M: How psychological stress via hormones and nerve fibers may exacerbate rheumatoid arthritis. Arthritis Rheum 2005;52:16–26.