Journal Mobile Options
Table of Contents
Vol. 14, No. 5, 2007
Issue release date: February 2008
Neuroimmunomodulation 2007;14:272–280
(DOI:10.1159/000115041)

Lymphocyte Subsets and the Role of Th1/Th2 Balance in Stressed Chronic Pain Patients

Kaufmann I. · Eisner C. · Richter P. · Huge V. · Beyer A. · Chouker A. · Schelling G. · Thiel M.
Department of Anesthesiology, Klinikum Grosshadern, Ludwig Maximilians University, Munich, Germany

Individual Users: Register with Karger 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

Abstract

Background: The complex regional pain syndrome (CRPS) and fibromyalgia (FM) are chronic pain syndromes occurring in highly stressed individuals. Despite the known connection between the nervous system and immune cells, information on distribution of lymphocyte subsets under stress and pain conditions is limited. Methods: We performed a comparative study in 15 patients with CRPS type I, 22 patients with FM and 37 age- and sex-matched healthy controls and investigated the influence of pain and stress on lymphocyte number, subpopulations and the Th1/Th2 cytokine ratio in T lymphocytes. Results: Lymphocyte numbers did not differ between groups. Quantitative analyses of lymphocyte subpopulations showed a significant reduction of cytotoxic CD8+ lymphocytes in both CRPS (p < 0.01) and FM (p < 0.05) patients as compared with healthy controls. Additionally, CRPS patients were characterized by a lower percentage of IL-2-producing T cell subpopulations reflecting a diminished Th1 response in contrast to no changes in the Th2 cytokine profile. Conclusions: Future studies are warranted to answer whether such immunological changes play a pathogenetic role in CRPS and FM or merely reflect the consequences of a pain-induced neurohumoral stress response, and whether they contribute to immunosuppression in stressed chronic pain patients.



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. Geertzen JH, Bruijn-Kofman AT, de Bruijn HP, van de Wiel HB, Dijkstra PU: Stressful life events and psychological dysfunction in complex regional pain syndrome type I. Clin J Pain 1998;14:143–147.
  2. Grande LA, Loeser JD, Ozuna J, Ashleigh A, Samii A: Complex regional pain syndrome as a stress response. Pain 2004;110:495–498.
  3. Hudson JI, Arnold LM, Keck PE Jr, Auchenbach MB, Pope HG: Family study of fibromyalgia and affective spectrum disorder. Biol Psychiatry 2004;56:884–891.
  4. McEwen BS: Physiology and neurobiology of stress and adaptation: central role of the brain. Physiol Rev 2007;87:873–904.
  5. Van Houdenhove B, Egle U, Luyten P: The role of life stress in fibromyalgia. Curr Rheumatol Rep 2005;7:365–370.
  6. Van Houdenhove B, Luyten P: Stress, depression and fibromyalgia. Acta Neurol Belg 2006;106:149–156.
  7. Walker EA, Keegan D, Gardner G, Sullivan M, Bernstein D, Katon WJ: Psychosocial factors in fibromyalgia compared with rheumatoid arthritis. 2. Sexual, physical, and emotional abuse and neglect. Psychosom Med 1997;59:572–577.
  8. Schwartzman RJ, Alexander GM, Grothusen J: Pathophysiology of complex regional pain syndrome. Expert Rev Neurother 2006;6:669–681.
  9. Yunus MB: Fibromyalgia and overlapping disorders: the unifying concept of central sensitivity syndromes. Semin Arthritis Rheum 2007;36:339–356.
  10. Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, Tugwell P, Campbell SM, Abeles M, Clark P, Fam AG, Farber SJ, Fiechtner JJ, Franklin CM, Gatter RA, Hamaty D, Lessard J, Lichtbroun AS, Masi AT, McCain GA, Reynolds WJ, Romano TJ, Russell IJ, Sheon RP: The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum 1990;33:160–172.
  11. Brogden KA, Guthmiller JM, Salzet M, Zasloff M: The nervous system and innate immunity: the neuropeptide connection. Nat Immunol 2005;6:558–564.
  12. Elenkov IJ, Wilder RL, Chrousos GP, Vizi ES: The sympathetic nerve – an integrative interface between two supersystems: the brain and the immune system. Pharmacol Rev 2000;52:595–638.
  13. Elenkov IJ, Iezzoni DG, Daly A, Harris AG, Chrousos GP: Cytokine dysregulation, inflammation and well-being. Neuroimmunomodulation 2005;12:255–269.
  14. Herbert TB, Cohen S: Stress and immunity in humans: a meta-analytic review. Psychosom Med 1993;55:364–379.
  15. Joachim RA, Sagach V, Quarcoo D, Dinh T, Arck PC, Klapp BF: Upregulation of tumor necrosis factor-alpha by stress and substance P in a murine model of allergic airway inflammation. Neuroimmunomodulation 2006;13:43–50.
  16. Kaufmann I, Eisner C, Richter P, Huge V, Beyer A, Chouker A, Schelling G, Thiel M: Psychoneuroendocrine stress response may impair neutrophil function in complex regional pain syndrome. Clin Immunol 2007;125:103–111.
  17. Marchand F, Perretti M, McMahon SB: Role of the immune system in chronic pain. Nat Rev Neurosci 2005;6:521–532.
  18. Tarcic N, Levitan G, Ben Yosef D, Prous D, Ovadia H, Weiss DW: Restraint stress-induced changes in lymphocyte subsets and the expression of adhesion molecules. Neuroimmunomodulation 1995;2:249–257.
  19. Stefanski V, Engler H: Social stress, dominance and blood cellular immunity. J Neuroimmunol 1999;94:144–152.
  20. Buske-Kirschbaum A, Kern S, Ebrecht M, Hellhammer DH: Altered distribution of leukocyte subsets and cytokine production in response to acute psychosocial stress in patients with psoriasis vulgaris. Brain Behav Immun 2007;21:92–99.
  21. Hennig J, Netter P, Voigt KH: Cortisol mediates redistribution of CD8+ but not of CD56+ cells after the psychological stress of public speaking. Psychoneuroendocrinology 2001;26:673–687.
  22. Sgoutas-Emch SA, Cacioppo JT, Uchino BN, Malarkey W, Pearl D, Kiecolt-Glaser JK, Glaser R: The effects of an acute psychological stressor on cardiovascular, endocrine, and cellular immune response: a prospective study of individuals high and low in heart rate reactivity. Psychophysiology 1994;31:264–271.
  23. Caggiula AR, McAllister CG, Matthews KA, Berga SL, Owens JF, Miller AL: Psychological stress and immunological responsiveness in normally cycling, follicular-stage women. J Neuroimmunol 1995;59:103–111.
  24. Vidovic A, Vilibic M, Sabioncello A, Gotovac K, Rabatic S, Folnegovic-Smalc V, Dekaris D: Circulating lymphocyte subsets, natural killer cell cytotoxicity, and components of hypothalamic-pituitary-adrenal axis in Croatian war veterans with posttraumatic stress disorder: cross-sectional study. Croat Med J 2007;48:198–206.
  25. Bussone G, Salmaggi A, Leone M, Valentini S, Dufour A, Nespolo A: Immunological alterations in cluster headache during remission and cluster period. Comparison with low back pain patients. Cephalalgia 1992;12:250–253.
  26. Leone M, Biffi M, Leoni F, Bussone G: Leukocyte subsets and cortisol serum levels in patients with migraine without aura and chronic tension-type headache. Cephalalgia 1994;14:139–142.
  27. Stanton-Hicks M, Jänig W, Hassenbusch S, Haddox JD, Boas R, Wilson P: Reflex sympathetic dystrophy – changing concepts and taxonomy. Pain 1995;63:127–133.
  28. Bruehl S, Harden RN, Galer BS, Saltz S, Bertram M, Backonja M, Gayles R, Rudin N, Bhugra MK, Stanton-Hicks M: External validation of IASP diagnostic criteria for complex regional pain syndrome and proposed research diagnostic criteria. Pain 1999;81:147–154.
  29. Stoll C, Kapfhammer HP, Rothenhausler HB, Haller M, Briegel J, Schmidt M, Krauseneck T, Durst K, Schelling G: Sensitivity and specificity of a screening test to document traumatic experiences and to diagnose post-traumatic stress disorder in ARDS patients after intensive care treatment. Intensive Care Med 1999;25:697–704.
  30. Weisaeth L: Torture of a Norwegian ship’s crew. The torture, stress reactions and psychiatric after-effects. Acta Psychiatr Scand Suppl 1989;355:63–72.
  31. Gilman-Sachs A, Robbins L, Baum L: Flow cytometric analysis of lymphocyte subsets in peripheral blood of chronic headache patients. Headache 1989;29:290–294.
  32. Milosevic DB: The different level of immunological recovery after chemotherapy in leukemia and lymphoma patients. J Exp Clin Cancer Res 2001;20:517–522.
  33. Smyth LJ, Elkord E, Taher TE, Jiang HR, Burt DJ, Clayton A, van Veelen PA, de Ru A, Ossendorp F, Melief CJ, Drijfhout JW, Dermime S, Hawkins RE, Stern PL: CD8 T-cell recognition of human 5T4 oncofetal antigen. Int J Cancer 2006;119:1638–1647.
  34. Reichenbach J, Schubert R, Horvath R, Petersen J, Futterer N, Malle E, Stumpf A, Gebhardt BR, Koehl U, Schraven B, Zielen S: Fatal neonatal-onset mitochondrial respiratory chain disease with T cell immunodeficiency. Pediatr Res 2006;60:321–326.
  35. Kubera M, Basta-Kaim A, Holan V, Simbirtsev A, Roman A, Pigareva N, Prokopieva E, Sham J: Effect of mild chronic stress, as a model of depression, on the immunoreactivity of C57BL/6 mice. Int J Immunopharmacol 1998;20:781–789.
  36. Avgustin B, Wraber B, Tavcar R: Increased Th-1 and Th-2 immune reactivity with relative Th-2 dominance in patients with acute exacerbation of schizophrenia. Croat Med J 2005;46:268–274.
  37. Liblau RS, Singer SM, McDevitt HO: Th1 and Th2 Cd4(+) T cells in the pathogenesis of organ-specific autoimmune diseases. Immunol Today 1995;16:34–38.
  38. Radstake TRDJ, van Lent PLEM, Pesman GJ, Blom AB, Sweep FGJ, Ronnelid J, Adema GJ, Barrera P, van den Berg WB: High production of proinflammatory and Th1 cytokines by dendritic cells from patients with rheumatoid arthritis, and down regulation upon Fc gamma R triggering. Ann Rheum Dis 2004;63:696–702.
  39. Smart JM, Suphioglu C, Kemp AS: Age-related T cell responses to allergens in childhood. Clin Exp Allergy 2003;33:317–324.
  40. Tournoy KG, Kips JC, Pauwels RA: The allergen-induced airway hyperresponsiveness in a human-mouse chimera model of asthma is T cell and IL-4 and IL-5 dependent. J Immunol 2001;166:6982–6991.
  41. Tournoy KG, Kips JC, Pauwels RA: Counterbalancing of T(H)2-driven allergic airway inflammation by IL-12 does not require IL-10. J Allergy Clin Immunol 2001;107:483–491.
  42. Sanders VM, Baker RA, Ramer-Quinn DS, Kasprowicz DJ, Fuchs BA, Street NE: Differential expression of the beta(2)-adrenergic receptor by Th1 and Th2 clones – implications for cytokine production and B cell help. J Immunol 1997;158:4200–4210.
  43. Woiciechowsky C, Asadullah K, Nestler D, Eberhardt B, Platzer C, Schoning B, Glockner F, Lanksch WR, Volk HD, Docke WD: Sympathetic activation triggers systemic interleukin-10 release in immunodepression induced by brain injury. Nat Med 1998;4:808–813.
  44. Woiciechowsky C, Volk HD: Increased intracranial pressure induces a rapid systemic interleukin-10 release through activation of the sympathetic nervous system. Acta Neurochir Suppl 2005;95:373–376.
  45. Harden RN, Rudin NJ, Bruehl S, Kee W, Parikh DK, Kooch J, Duc T, Gracely RH: Increased systemic catecholamines in complex regional pain syndrome and relationship to psychological factors: a pilot study. Anesth Analg 2004;99:1478–1485.
  46. Hamaty D, Valentine JL, Howard R, Howard CW, Wakefield V, Patten MS: The plasma endorphin, prostaglandin and catecholamine profile of patients with fibrositis treated with cyclobenzaprine and placebo: a 5-month study. J Rheumatol Suppl 1989;19:164–168.
  47. Tsatsoulis A: The role of stress in the clinical expression of thyroid autoimmunity. Ann NY Acad Sci 2006;1088:382–395.
  48. Pamuk ON, Cakir N: The frequency of thyroid antibodies in fibromyalgia patients and their relationship with symptoms. Clin Rheumatol 2007;26:55–59.
  49. Gage JR, Fonarow G, Hamilton M, Widawski M, Martinez-Maza O, Vredevoe DL: Beta blocker and angiotensin-converting enzyme inhibitor therapy is associated with decreased Th1/Th2 cytokine ratios and inflammatory cytokine production in patients with chronic heart failure. Neuroimmunomodulation 2004;11:173–180.
  50. Constant SL, Bottomly K: Induction of Th1 and Th2 CD4+ T cell responses: the alternative approaches. Annu Rev Immunol 1997;15:297–322.
  51. Schinkel C, Gaertner A, Zaspel J, Zedler S, Faist E, Schuermann M: Inflammatory mediators are altered in the acute phase of posttraumatic complex regional pain syndrome. Clin J Pain 2006;22:235–239.
  52. Van de Vusse AC, Goossens VJ, Kemler MA, Weber WEJ: Screening of patients with complex regional pain syndrome for antecedent infections. Clin J Pain 2001;17:110–114.
  53. Sarzi-Puttini P, Atzeni F, Diana A, Doria A, Furlan R: Increased neural sympathetic activation in fibromyalgia syndrome. Ann NY Acad Sci 2006;1069:109–117.
  54. Li M, Wang Y, Guo R, Bai Y, Yu Z: Glucocorticoids impair microglia ability to induce T cell proliferation and Th1 polarization. Immunol Lett 2007;109:129–137.
  55. Okada M, Suzuki K, Hidaka T, Shinohara T, Kataharada K, Takada K, Tanaka H, Ohsuzu F: Complex regional pain syndrome type I induced by pacemaker implantation, with a good response to steroids and neurotropin. Intern Med 2002;41:498–501.
  56. Marx C, Petros S, Bornstein SR, Wiese M, Wendt M, Menschikowski M, Engelmann L, Höffken G: Adrenocortical hormones in survivors and nonsurvivors of severe sepsis: diverse time course of dehydroepiandrosterone, dehydroepiandrosterone-sulfate and cortisol. Crit Care Med 2003;31:1382–1388.
  57. Maggio M, Ceda GP, Denti L, Rebecchi I, Manganelli P, Ablondi F, Valenti G: Decreased DHEAS secretion in patients with chronic inflammatory diseases treated with glucocorticoids. J Endocrinol Invest 2002;25(10 suppl):87–88.
  58. Powell JM, Sonnenfeld G: The effects of dehydroepiandrosterone (DHEA) on in vitro spleen cell proliferation and cytokine production. J Interferon Cytokine Res 2006;26:34–39.
  59. Sacerdote P: Opiods and the immune system. Palliat Med 2006;20(suppl 1):S9–S15.

    External Resources

  60. Karlsson H, Gu Y, DePierre J, Nässberger L: Induction of apoptosis in proliferating lymphocytes by tricyclic antidepressants. Apoptosis 1998;3:255–260.


Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50