Journal of Neurology

, Volume 258, Issue 4, pp 533–548 | Cite as

The role of cytokines in Guillain–Barré syndrome

Review

Abstract

Cytokines play an important role in the pathogenesis of autoimmune diseases including Guillain–Barré syndrome (GBS) and its animal model experimental autoimmune neuritis (EAN). In this article, we reviewed the current knowledge of the role of cytokines such as TNF-α, IFN-γ, IL-1β, IL-6, IL-12, IL-18, IL-23, IL-17, IL-10, IL-4 and chemokines in GBS and EAN as unraveled by studies both in the clinic and the laboratory. However, these studies occasionally yield conflicting results, highlighting the complex role that cytokines play in the disease process. Efforts to modulate cytokine function in GBS and other autoimmune disease have shown efficiency indicating that cytokines are important therapeutic targets.

Keywords

Cytokine Guillain–Barré syndrome Experimental autoimmune neuritis Autoimmunity T cell 

References

  1. 1.
    van Doorn PA, Ruts L, Jacobs BC (2008) Clinical features, pathogenesis, and treatment of Guillain–Barre syndrome. Lancet Neurol 7:939–950PubMedGoogle Scholar
  2. 2.
    Griffin JW, Li CY, Ho TW, Xue P, Macko C, Gao CY, Yang C, Tian M, Mishu B, Cornblath DR (1995) Guillain–Barre syndrome in northern China. The spectrum of neuropathological changes in clinically defined cases. Brain 118(Pt 3):577–595PubMedGoogle Scholar
  3. 3.
    Fisher M (1956) An unusual variant of acute idiopathic polyneuritis (syndrome of ophthalmoplegia, ataxia and areflexia). N Engl J Med 255:57–65PubMedGoogle Scholar
  4. 4.
    Yuki N (2007) Ganglioside mimicry and peripheral nerve disease. Muscle Nerve 35:691–711PubMedGoogle Scholar
  5. 5.
    Vucic S, Kiernan MC, Cornblath DR (2009) Guillain–Barre syndrome: an update. J Clin Neurosci 16:733–741PubMedGoogle Scholar
  6. 6.
    Hughes RA, Hadden RD, Gregson NA, Smith KJ (1999) Pathogenesis of Guillain–Barre syndrome. J Neuroimmunol 100:74–97PubMedGoogle Scholar
  7. 7.
    Willison HJ, Yuki N (2002) Peripheral neuropathies and anti-glycolipid antibodies. Brain 125:2591–2625PubMedGoogle Scholar
  8. 8.
    Hughes RA, Swan AV, Raphael JC, Annane D, van Koningsveld R, van Doorn PA (2007) Immunotherapy for Guillain–Barre syndrome: a systematic review. Brain 130:2245–2257PubMedGoogle Scholar
  9. 9.
    Hahn AF (1998) Guillain–Barre syndrome. Lancet 352:635–641PubMedGoogle Scholar
  10. 10.
    Hughes RA, Swan AV, van Koningsveld R, van Doorn PA (2006) Corticosteroids for Guillain–Barre syndrome. Cochrane Database Syst Rev: CD001446Google Scholar
  11. 11.
    van der Meche FG, Schmitz PI (1992) A randomized trial comparing intravenous immune globulin and plasma exchange in Guillain–Barre syndrome. Dutch Guillain–Barre Study Group. N Engl J Med 326:1123–1129PubMedGoogle Scholar
  12. 12.
    Zhu J, Mix E, Link H (1998) Cytokine production and the pathogenesis of experimental autoimmune neuritis and Guillain–Barre syndrome. J Neuroimmunol 84:40–52PubMedGoogle Scholar
  13. 13.
    Zhu J, Bai XF, Mix E, Link H (1997) Cytokine dichotomy in peripheral nervous system influences the outcome of experimental allergic neuritis: dynamics of mRNA expression for IL-1 beta, IL-6, IL-10, IL-12, TNF-alpha, TNF-beta, and cytolysin. Clin Immunol Immunopathol 84:85–94PubMedGoogle Scholar
  14. 14.
    Yu S, Chen Z, Mix E, Zhu SW, Winblad B, Ljunggren HG, Zhu J (2002) Neutralizing antibodies to IL-18 ameliorate experimental autoimmune neuritis by counter-regulation of autoreactive Th1 responses to peripheral myelin antigen. J Neuropathol Exp Neurol 61:614–622PubMedGoogle Scholar
  15. 15.
    Nicoletti F, Creange A, Orlikowski D, Bolgert F, Mangano K, Metz C, Di Marco R, Al Abed Y (2005) Macrophage migration inhibitory factor (MIF) seems crucially involved in Guillain–Barre syndrome and experimental allergic neuritis. J Neuroimmunol 168:168–174PubMedGoogle Scholar
  16. 16.
    Bao L, Lindgren JU, van der Meide P, Zhu S, Ljunggren HG, Zhu J (2002) The critical role of IL-12p40 in initiating, enhancing, and perpetuating pathogenic events in murine experimental autoimmune neuritis. Brain Pathol 12:420–429PubMedGoogle Scholar
  17. 17.
    Kiefer R, Funa K, Schweitzer T, Jung S, Bourde O, Toyka KV, Hartung HP (1996) Transforming growth factor-beta 1 in experimental autoimmune neuritis. Cellular localization and time course. Am J Pathol 148:211–223PubMedGoogle Scholar
  18. 18.
    Deretzi G, Pelidou S, Zou L, Quiding C, Mix E, Levi M, Wahren B, Zhu J (1999) Suppression of chronic experimental autoimmune neuritis by nasally administered recombinant rat interleukin-6. Immunology 97:69–76PubMedGoogle Scholar
  19. 19.
    Bai XF, Zhu J, Zhang GX, Kaponides G, Hojeberg B, van der Meide PH, Link H (1997) IL-10 suppresses experimental autoimmune neuritis and down-regulates TH1-type immune responses. Clin Immunol Immunopathol 83:117–126PubMedGoogle Scholar
  20. 20.
    Li MO, Wan YY, Flavell RA (2007) T cell-produced transforming growth factor-beta1 controls T cell tolerance and regulates Th1- and Th17-cell differentiation. Immunity 26:579–591PubMedGoogle Scholar
  21. 21.
    McGeachy MJ, Cua DJ (2007) T cells doing it for themselves: TGF-beta regulation of Th1 and Th17 cells. Immunity 26:547–549PubMedGoogle Scholar
  22. 22.
    Harness J, McCombe PA (2008) Increased levels of activated T-cells and reduced levels of CD4/CD25+ cells in peripheral blood of Guillain–Barre syndrome patients compared to controls. J Clin Neurosci 15:1031–1035PubMedGoogle Scholar
  23. 23.
    Chi LJ, Wang HB, Zhang Y, Wang WZ (2007) Abnormality of circulating CD4(+)CD25(+) regulatory T cell in patients with Guillain–Barre syndrome. J Neuroimmunol 192:206–214PubMedGoogle Scholar
  24. 24.
    Schmidt B, Stoll G, van der Meide P, Jung S, Hartung HP (1992) Transient cellular expression of gamma-interferon in myelin-induced and T-cell line-mediated experimental autoimmune neuritis. Brain 115(Pt 6):1633–1646PubMedGoogle Scholar
  25. 25.
    Girkontaite I, Urbonaviciute V, Maseda D, Neubert K, Herrmann M, Voll RE (2007) Apoptotic cells selectively suppress the Th1 cytokine interferon gamma in stimulated human peripheral blood mononuclear cells and shift the Th1/Th2 balance towards Th2. Autoimmunity 40:327–330PubMedGoogle Scholar
  26. 26.
    Gold R, Zielasek J, Kiefer R, Toyka KV, Hartung HP (1996) Secretion of nitrite by Schwann cells and its effect on T-cell activation in vitro. Cell Immunol 168:69–77PubMedGoogle Scholar
  27. 27.
    Gold R, Toyka KV, Hartung HP (1995) Synergistic effect of IFN-gamma and TNF-alpha on expression of immune molecules and antigen presentation by Schwann cells. Cell Immunol 165:65–70PubMedGoogle Scholar
  28. 28.
    Zhu Y, Ljunggren HG, Mix E, Li HL, van der Meide P, Elhassan AM, Winblad B, Zhu J (2001) Suppression of autoimmune neuritis in IFN-gamma receptor-deficient mice. Exp Neurol 169:472–478PubMedGoogle Scholar
  29. 29.
    Hohnoki K, Inoue A, Koh CS (1998) Elevated serum levels of IFN-gamma, IL-4 and TNF-alpha/unelevated serum levels of IL-10 in patients with demyelinating diseases during the acute stage. J Neuroimmunol 87:27–32PubMedGoogle Scholar
  30. 30.
    Csurhes PA, Sullivan AA, Green K, Greer JM, Pender MP, McCombe PA (2005) Increased circulating T cell reactivity to GM1 ganglioside in patients with Guillain–Barre syndrome. J Clin Neurosci 12:409–415PubMedGoogle Scholar
  31. 31.
    Elkarim RA, Dahle C, Mustafa M, Press R, Zou LP, Ekerfelt C, Ernerudh J, Link H, Bakhiet M (1998) Recovery from Guillain–Barre syndrome is associated with increased levels of neutralizing autoantibodies to interferon-gamma. Clin Immunol Immunopathol 88:241–248PubMedGoogle Scholar
  32. 32.
    Chu CQ, Wittmer S, Dalton DK (2000) Failure to suppress the expansion of the activated CD4 T cell population in interferon gamma-deficient mice leads to exacerbation of experimental autoimmune encephalomyelitis. J Exp Med 192:123–128PubMedGoogle Scholar
  33. 33.
    Jones LS, Rizzo LV, Agarwal RK, Tarrant TK, Chan CC, Wiggert B, Caspi RR (1997) IFN-gamma-deficient mice develop experimental autoimmune uveitis in the context of a deviant effector response. J Immunol 158:5997–6005PubMedGoogle Scholar
  34. 34.
    Kelchtermans H, Struyf S, De Klerck B, Mitera T, Alen M, Geboes L, Van Balen M, Dillen C, Put W, Gysemans C, Billiau A, Van Damme J, Matthys P (2007) Protective role of IFN-gamma in collagen-induced arthritis conferred by inhibition of mycobacteria-induced granulocyte chemotactic protein-2 production. J Leukoc Biol 81:1044–1053PubMedGoogle Scholar
  35. 35.
    Nicoletti F, Zaccone P, Di Marco R, Magro G, Grasso S, Stivala F, Calori G, Mughini L, Meroni PL, Garotta G (1998) Paradoxical antidiabetogenic effect of gamma-interferon in DP-BB rats. Diabetes 47:32–38PubMedGoogle Scholar
  36. 36.
    Sobel DO, Newsome J (1997) Gamma interferon prevents diabetes in the BB rat. Clin Diagn Lab Immunol 4:764–768PubMedGoogle Scholar
  37. 37.
    Sobel DO, Han J, Williams J, Yoon JW, Jun HS, Ahvazi B (2002) Gamma interferon paradoxically inhibits the development of diabetes in the NOD mouse. J Autoimmun 19:129–137PubMedGoogle Scholar
  38. 38.
    (1992) Double blind controlled phase III multicenter clinical trial with interferon gamma in rheumatoid arthritis. German Lymphokine Study Group. Rheumatol Int 12:175–185Google Scholar
  39. 39.
    Machold KP, Neumann K, Smolen JS (1992) Recombinant human interferon gamma in the treatment of rheumatoid arthritis: double blind placebo controlled study. Ann Rheum Dis 51:1039–1043PubMedGoogle Scholar
  40. 40.
    Sigidin YA, Loukina GV, Skurkovich B, Skurkovich S (2001) Randomized, double-blind trial of anti-interferon-gamma antibodies in rheumatoid arthritis. Scand J Rheumatol 30:203–207PubMedGoogle Scholar
  41. 41.
    Kelchtermans H, Billiau A, Matthys P (2008) How interferon-gamma keeps autoimmune diseases in check. Trends Immunol 29:479–486PubMedGoogle Scholar
  42. 42.
    Su SB, Grajewski RS, Luger D, Agarwal RK, Silver PB, Tang J, Tuo J, Chan CC, Caspi RR (2007) Altered chemokine profile associated with exacerbated autoimmune pathology under conditions of genetic interferon-gamma deficiency. Invest Ophthalmol Vis Sci 48:4616–4625PubMedGoogle Scholar
  43. 43.
    Wang Z, Hong J, Sun W, Xu G, Li N, Chen X, Liu A, Xu L, Sun B, Zhang JZ (2006) Role of IFN-gamma in induction of Foxp3 and conversion of CD4+ CD25− T cells to CD4+ Tregs. J Clin Invest 116:2434–2441PubMedGoogle Scholar
  44. 44.
    Luger D, Silver PB, Tang J, Cua D, Chen Z, Iwakura Y, Bowman EP, Sgambellone NM, Chan CC, Caspi RR (2008) Either a Th17 or a Th1 effector response can drive autoimmunity: conditions of disease induction affect dominant effector category. J Exp Med 205:799–810PubMedGoogle Scholar
  45. 45.
    Kelchtermans H, Schurgers E, Geboes L, Mitera T, Van Damme J, Van Snick J, Uyttenhove C, Matthys P (2009) Effector mechanisms of interleukin-17 in collagen-induced arthritis in the absence of interferon-gamma and counteraction by interferon-gamma. Arthritis Res Ther 11:R122PubMedGoogle Scholar
  46. 46.
    Shaked I, Tchoresh D, Gersner R, Meiri G, Mordechai S, Xiao X, Hart RP, Schwartz M (2005) Protective autoimmunity: interferon-gamma enables microglia to remove glutamate without evoking inflammatory mediators. J Neurochem 92:997–1009PubMedGoogle Scholar
  47. 47.
    Schwartz M, Butovsky O, Kipnis J (2006) Does inflammation in an autoimmune disease differ from inflammation in neurodegenerative diseases? Possible implications for therapy. J Neuroimmune Pharmacol 1:4–10PubMedGoogle Scholar
  48. 48.
    Shaked I, Porat Z, Gersner R, Kipnis J, Schwartz M (2004) Early activation of microglia as antigen-presenting cells correlates with T cell-mediated protection and repair of the injured central nervous system. J Neuroimmunol 146:84–93PubMedGoogle Scholar
  49. 49.
    Foulds KE, Rotte MJ, Paley MA, Singh B, Douek DC, Hill BJ, O’Shea JJ, Watford WT, Seder RA, Wu CY (2008) IFN-gamma mediates the death of Th1 cells in a paracrine manner. J Immunol 180:842–849PubMedGoogle Scholar
  50. 50.
    Huang S, Li L, Liang S, Wang W (2009) Conversion of peripheral CD4(+)CD25(−) T cells to CD4(+)CD25(+) regulatory T cells by IFN-gamma in patients with Guillain–Barre syndrome. J Neuroimmunol 217:80–84PubMedGoogle Scholar
  51. 51.
    Murwani R, Hodgkinson S, Armati P (1996) Tumor necrosis factor alpha and interleukin-6 mRNA expression in neonatal Lewis rat Schwann cells and a neonatal rat Schwann cell line following interferon gamma stimulation. J Neuroimmunol 71:65–71PubMedGoogle Scholar
  52. 52.
    Bao L, Lindgren JU, Zhu Y, Ljunggren HG, Zhu J (2003) Exogenous soluble tumor necrosis factor receptor type I ameliorates murine experimental autoimmune neuritis. Neurobiol Dis 12:73–81PubMedGoogle Scholar
  53. 53.
    Smith CA, Farrah T, Goodwin RG (1994) The TNF receptor superfamily of cellular and viral proteins: activation, costimulation, and death. Cell 76:959–962PubMedGoogle Scholar
  54. 54.
    Shubayev VI, Angert M, Dolkas J, Campana WM, Palenscar K, Myers RR (2006) TNFalpha-induced MMP-9 promotes macrophage recruitment into injured peripheral nerve. Mol Cell Neurosci 31:407–415PubMedGoogle Scholar
  55. 55.
    Cheng C, Qin Y, Shao X, Wang H, Gao Y, Cheng M, Shen A (2007) Induction of TNF-alpha by LPS in Schwann cell is regulated by MAPK activation signals. Cell Mol Neurobiol 27:909–921PubMedGoogle Scholar
  56. 56.
    Myers RR, Sekiguchi Y, Kikuchi S, Scott B, Medicherla S, Protter A, Campana WM (2003) Inhibition of p38 MAP kinase activity enhances axonal regeneration. Exp Neurol 184:606–614PubMedGoogle Scholar
  57. 57.
    Boyle K, Azari MF, Cheema SS, Petratos S (2005) TNFalpha mediates Schwann cell death by upregulating p75NTR expression without sustained activation of NFkappaB. Neurobiol Dis 20:412–427PubMedGoogle Scholar
  58. 58.
    Tao T, Ji Y, Cheng C, Yang H, Liu H, Sun L, Qin Y, Yang J, Wang H, Shen A (2009) Tumor necrosis factor-alpha inhibits Schwann cell proliferation by up-regulating Src-suppressed protein kinase C substrate expression. J Neurochem 111:647–655PubMedGoogle Scholar
  59. 59.
    Evangelidou M, Tseveleki V, Vamvakas SS, Probert L (2010) TNFRI is a positive T-cell costimulatory molecule important for the timing of cytokine responses. Immunol Cell Biol 88:586–595PubMedGoogle Scholar
  60. 60.
    Radhakrishnan VV, Sumi MG, Reuben S, Mathai A, Nair MD (2004) Serum tumour necrosis factor-alpha and soluble tumour necrosis factor receptors levels in patients with Guillain–Barre syndrome. Acta Neurol Scand 109:71–74PubMedGoogle Scholar
  61. 61.
    Zhang J, Dong H, Li B, Li CY, Guo L (2007) Association of tumor necrosis factor polymorphisms with Guillain–Barre syndrome. Eur Neurol 58:21–25PubMedGoogle Scholar
  62. 62.
    Kurz M, Pischel H, Hartung HP, Kieseier BC (2005) Tumor necrosis factor-alpha-converting enzyme is expressed in the inflamed peripheral nervous system. J Peripher Nerv Syst 10:311–318PubMedGoogle Scholar
  63. 63.
    Sharief MK, Ingram DA, Swash M, Thompson EJ (1999) I.v. immunoglobulin reduces circulating proinflammatory cytokines in Guillain–Barre syndrome. Neurology 52:1833–1838PubMedGoogle Scholar
  64. 64.
    Deng H, Yang X, Jin T, Wu J, Hu LS, Chang M, Sun XJ, Adem A, Winblad B, Zhu J (2008) The role of IL-12 and TNF-alpha in AIDP and AMAN. Eur J Neurol 15:1100–1105PubMedGoogle Scholar
  65. 65.
    Ruiz de Souza V, Carreno MP, Kaveri SV, Ledur A, Sadeghi H, Cavaillon JM, Kazatchkine MD, Haeffner-Cavaillon N (1995) Selective induction of interleukin-1 receptor antagonist and interleukin-8 in human monocytes by normal polyspecific IgG (intravenous immunoglobulin). Eur J Immunol 25:1267–1273PubMedGoogle Scholar
  66. 66.
    Mao XJ, Zhang XM, Zhang HL, Quezada HC, Mix E, Yang X, Winblad B, Adem A, Zhu J (2010) TNF-alpha receptor 1 deficiency reduces antigen-presenting capacity of Schwann cells and ameliorates experimental autoimmune neuritis in mice. Neurosci Lett 470:19–23PubMedGoogle Scholar
  67. 67.
    Taylor JM, Pollard JD (2007) Soluble TNFR1 inhibits the development of experimental autoimmune neuritis by modulating blood-nerve-barrier permeability and inflammation. J Neuroimmunol 183:118–124PubMedGoogle Scholar
  68. 68.
    Campana WM (2007) Schwann cells: activated peripheral glia and their role in neuropathic pain. Brain Behav Immun 21:522–527PubMedGoogle Scholar
  69. 69.
    Moalem-Taylor G, Allbutt HN, Iordanova MD, Tracey DJ (2007) Pain hypersensitivity in rats with experimental autoimmune neuritis, an animal model of human inflammatory demyelinating neuropathy. Brain Behav Immun 21:699–710PubMedGoogle Scholar
  70. 70.
    Campana WM, Li X, Shubayev VI, Angert M, Cai K, Myers RR (2006) Erythropoietin reduces Schwann cell TNF-alpha, Wallerian degeneration and pain-related behaviors after peripheral nerve injury. Eur J Neurosci 23:617–626PubMedGoogle Scholar
  71. 71.
    Creange A, Belec L, Clair B, Raphael JC, Gherardi RK (1996) Circulating tumor necrosis factor (TNF)-alpha and soluble TNF-alpha receptors in patients with Guillain–Barre syndrome. J Neuroimmunol 68:95–99PubMedGoogle Scholar
  72. 72.
    Weishaupt A, Gold R, Hartung T, Gaupp S, Wendel A, Bruck W, Toyka KV (2000) Role of TNF-alpha in high-dose antigen therapy in experimental autoimmune neuritis: inhibition of TNF-alpha by neutralizing antibodies reduces T-cell apoptosis and prevents liver necrosis. J Neuropathol Exp Neurol 59:368–376PubMedGoogle Scholar
  73. 73.
    Lu MO, Duan RS, Quezada HC, Chen ZG, Mix E, Jin T, Yang X, Ljunggren HG, Zhu J (2007) Aggravation of experimental autoimmune neuritis in TNF-alpha receptor 1 deficient mice. J Neuroimmunol 186:19–26PubMedGoogle Scholar
  74. 74.
    Lu MO, Zhang XM, Mix E, Quezada HC, Jin T, Zhu J, Adem A (2008) TNF-alpha receptor 1 deficiency enhances kainic acid-induced hippocampal injury in mice. J Neurosci Res 86:1608–1614PubMedGoogle Scholar
  75. 75.
    van Oosten BW, Barkhof F, Truyen L, Boringa JB, Bertelsmann FW, von Blomberg BM, Woody JN, Hartung HP, Polman CH (1996) Increased MRI activity and immune activation in two multiple sclerosis patients treated with the monoclonal anti-tumor necrosis factor antibody cA2. Neurology 47:1531–1534PubMedGoogle Scholar
  76. 76.
    Chen X, Baumel M, Mannel DN, Howard OM, Oppenheim JJ (2007) Interaction of TNF with TNF receptor type 2 promotes expansion and function of mouse CD4+CD25+ T regulatory cells. J Immunol 179:154–161PubMedGoogle Scholar
  77. 77.
    Chen X, Oppenheim JJ (2010) TNF-alpha: an activator of CD4+FoxP3+TNFR2+ regulatory T cells. Curr Dir Autoimmun 11:119–134PubMedGoogle Scholar
  78. 78.
    Nagar M, Jacob-Hirsch J, Vernitsky H, Berkun Y, Ben-Horin S, Amariglio N, Bank I, Kloog Y, Rechavi G, Goldstein I (2010) TNF activates a NF-kappaB-regulated cellular program in human CD45RA-regulatory T cells that modulates their suppressive function. J Immunol 184:3570–3581PubMedGoogle Scholar
  79. 79.
    Del Vecchio M, Bajetta E, Canova S, Lotze MT, Wesa A, Parmiani G, Anichini A (2007) Interleukin-12: biological properties and clinical application. Clin Cancer Res 13:4677–4685PubMedGoogle Scholar
  80. 80.
    Brahmachari S, Pahan K (2009) Suppression of regulatory T cells by IL-12p40 homodimer via nitric oxide. J Immunol 183:2045–2058PubMedGoogle Scholar
  81. 81.
    Calida DM, Kremlev SG, Fujioka T, Hilliard B, Ventura E, Constantinescu CS, Lavi E, Rostami A (2000) Experimental allergic neuritis in the SJL/J mouse: induction of severe and reproducible disease with bovine peripheral nerve myelin and pertussis toxin with or without interleukin-12. J Neuroimmunol 107:1–7PubMedGoogle Scholar
  82. 82.
    Pelidou SH, Zou LP, Deretzi G, Nennesmo I, Wei L, Mix E, Van Der Meide PH, Zhu J (2000) Intranasal administration of recombinant mouse interleukin-12 increases inflammation and demyelination in chronic experimental autoimmune neuritis in Lewis rats. Scand J Immunol 51:29–35PubMedGoogle Scholar
  83. 83.
    Press R, Ozenci V, Kouwenhoven M, Link H (2002) Non-T(H)1 cytokines are augmented systematically early in Guillain–Barre syndrome. Neurology 58:476–478PubMedGoogle Scholar
  84. 84.
    Cua DJ, Sherlock J, Chen Y, Murphy CA, Joyce B, Seymour B, Lucian L, To W, Kwan S, Churakova T, Zurawski S, Wiekowski M, Lira SA, Gorman D, Kastelein RA, Sedgwick JD (2003) Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 421:744–748PubMedGoogle Scholar
  85. 85.
    Goriely S, Neurath MF, Goldman M (2008) How microorganisms tip the balance between interleukin-12 family members. Nat Rev Immunol 8:81–86PubMedGoogle Scholar
  86. 86.
    Touil T, Fitzgerald D, Zhang GX, Rostami AM, Gran B (2006) Pathophysiology of interleukin-23 in experimental autoimmune encephalomyelitis. Drug News Perspect 19:77–83PubMedGoogle Scholar
  87. 87.
    Hu W, Dehmel T, Pirhonen J, Hartung HP, Kieseier BC (2006) Interleukin 23 in acute inflammatory demyelination of the peripheral nerve. Arch Neurol 63:858–864PubMedGoogle Scholar
  88. 88.
    Yoshida H, Nakaya M, Miyazaki Y (2009) Interleukin 27: a double-edged sword for offense and defense. J Leukoc Biol 86:1295–1303PubMedGoogle Scholar
  89. 89.
    Gee K, Guzzo C, Che Mat NF, Ma W, Kumar A (2009) The IL-12 family of cytokines in infection, inflammation and autoimmune disorders. Inflamm Allergy Drug Targets 8:40–52PubMedGoogle Scholar
  90. 90.
    Armati PJ, Pollard JD (1996) Immunology of the Schwann cell. Baillieres Clin Neurol 5:47–64PubMedGoogle Scholar
  91. 91.
    Conti G, De Pol A, Scarpini E, Vaccina F, De Riz M, Baron P, Tiriticco M, Scarlato G (2002) Interleukin-1 beta and interferon-gamma induce proliferation and apoptosis in cultured Schwann cells. J Neuroimmunol 124:29–35PubMedGoogle Scholar
  92. 92.
    Wolf G, Gabay E, Tal M, Yirmiya R, Shavit Y (2006) Genetic impairment of interleukin-1 signaling attenuates neuropathic pain, autotomy, and spontaneous ectopic neuronal activity, following nerve injury in mice. Pain 120:315–324PubMedGoogle Scholar
  93. 93.
    Hayashi R, Xiao W, Kawamoto M, Yuge O, Bennett GJ (2008) Systemic glucocorticoid therapy reduces pain and the number of endoneurial tumor necrosis factor-alpha (TNFalpha)-positive mast cells in rats with a painful peripheral neuropathy. J Pharmacol Sci 106:559–565PubMedGoogle Scholar
  94. 94.
    Sivieri S, Ferrarini AM, Lolli F, Mata S, Pinto F, Tavolato B, Gallo P (1997) Cytokine pattern in the cerebrospinal fluid from patients with GBS and CIDP. J Neurol Sci 147:93–95PubMedGoogle Scholar
  95. 95.
    Hartung HP, Reiners K, Schmidt B, Stoll G, Toyka KV (1991) Serum interleukin-2 concentrations in Guillain–Barre syndrome and chronic idiopathic demyelinating polyradiculoneuropathy: comparison with other neurological diseases of presumed immunopathogenesis. Ann Neurol 30:48–53PubMedGoogle Scholar
  96. 96.
    Felderhoff-Mueser U, Schmidt OI, Oberholzer A, Buhrer C, Stahel PF (2005) IL-18: a key player in neuroinflammation and neurodegeneration? Trends Neurosci 28:487–493PubMedGoogle Scholar
  97. 97.
    Nakanishi K, Yoshimoto T, Tsutsui H, Okamura H (2001) Interleukin-18 regulates both Th1 and Th2 responses. Annu Rev Immunol 19:423–474PubMedGoogle Scholar
  98. 98.
    Jander S, Stoll G (2001) Interleukin-18 is induced in acute inflammatory demyelinating polyneuropathy. J Neuroimmunol 114:253–258PubMedGoogle Scholar
  99. 99.
    Duan RS, Zhang XM, Mix E, Quezada HC, Adem A, Zhu J (2007) IL-18 deficiency inhibits both Th1 and Th2 cytokine production but not the clinical symptoms in experimental autoimmune neuritis. J Neuroimmunol 183:162–167PubMedGoogle Scholar
  100. 100.
    Kallen KJ (2002) The role of transsignalling via the agonistic soluble IL-6 receptor in human diseases. Biochim Biophys Acta 1592:323–343PubMedGoogle Scholar
  101. 101.
    Tofaris GK, Patterson PH, Jessen KR, Mirsky R (2002) Denervated Schwann cells attract macrophages by secretion of leukemia inhibitory factor (LIF) and monocyte chemoattractant protein-1 in a process regulated by interleukin-6 and LIF. J Neurosci 22:6696–6703PubMedGoogle Scholar
  102. 102.
    Zhu J, Link H, Weerth S, Linington C, Mix E, Qiao J (1994) The B cell repertoire in experimental allergic neuritis involves multiple myelin proteins and GM1. J Neurol Sci 125:132–137PubMedGoogle Scholar
  103. 103.
    Dominitzki S, Fantini MC, Neufert C, Nikolaev A, Galle PR, Scheller J, Monteleone G, Rose-John S, Neurath MF, Becker C (2007) Cutting edge: trans-signaling via the soluble IL-6R abrogates the induction of FoxP3 in naive CD4+CD25 T cells. J Immunol 179:2041–2045PubMedGoogle Scholar
  104. 104.
    Oukka M (2007) Interplay between pathogenic Th17 and regulatory T cells. Ann Rheum Dis 66(Suppl 3):iii87–iii90PubMedGoogle Scholar
  105. 105.
    Uceyler N, Sommer C (2008) Cytokine regulation in animal models of neuropathic pain and in human diseases. Neurosci Lett 437:194–198PubMedGoogle Scholar
  106. 106.
    Weller M, Stevens A, Sommer N, Melms A, Dichgans J, Wietholter H (1991) Comparative analysis of cytokine patterns in immunological, infectious, and oncological neurological disorders. J Neurol Sci 104:215–221PubMedGoogle Scholar
  107. 107.
    Deretzi G, Pelidou SH, Zou LP, Quiding C, Zhu J (1999) Local effects of recombinant rat interleukin-6 on the peripheral nervous system. Immunology 97:582–587PubMedGoogle Scholar
  108. 108.
    Choy DS, Black W, April R, Goldfinger G (2008) The Black–Choy sign. Photomed Laser Surg 26:273PubMedGoogle Scholar
  109. 109.
    Nishimoto N, Kishimoto T (2008) Humanized antihuman IL-6 receptor antibody, tocilizumab. Handb Exp Pharmacol 181:151–160Google Scholar
  110. 110.
    Rose-John S, Waetzig GH, Scheller J, Grotzinger J, Seegert D (2007) The IL-6/sIL-6R complex as a novel target for therapeutic approaches. Expert Opin Ther Targets 11:613–624PubMedGoogle Scholar
  111. 111.
    Andriambeloson E, Baillet C, Vitte PA, Garotta G, Dreano M, Callizot N (2006) Interleukin-6 attenuates the development of experimental diabetes-related neuropathy. Neuropathology 26:32–42PubMedGoogle Scholar
  112. 112.
    Ito T, Ikeda K, Tomita K, Yokoyama S (2010) Interleukin-6 upregulates the expression of PMP22 in cultured rat Schwann cells via a JAK2-dependent pathway. Neurosci Lett 472:104–108PubMedGoogle Scholar
  113. 113.
    Lara-Ramirez R, Segura-Anaya E, Martinez-Gomez A, Dent MA (2008) Expression of interleukin-6 receptor alpha in normal and injured rat sciatic nerve. Neuroscience 152:601–608PubMedGoogle Scholar
  114. 114.
    Knupfer H, Preiss R (2008) sIL-6R: more than an agonist? Immunol Cell Biol 86:87–91PubMedGoogle Scholar
  115. 115.
    Kunz M, Ibrahim SM (2009) Cytokines and cytokine profiles in human autoimmune diseases and animal models of autoimmunity. Mediators Inflamm 2009:979258PubMedGoogle Scholar
  116. 116.
    Yu JJ, Gaffen SL (2008) Interleukin-17: a novel inflammatory cytokine that bridges innate and adaptive immunity. Front Biosci 13:170–177PubMedGoogle Scholar
  117. 117.
    Zrioual S, Ecochard R, Tournadre A, Lenief V, Cazalis MA, Miossec P (2009) Genome-wide comparison between IL-17A- and IL-17F-induced effects in human rheumatoid arthritis synoviocytes. J Immunol 182:3112–3120PubMedGoogle Scholar
  118. 118.
    Doreau A, Belot A, Bastid J, Riche B, Trescol-Biemont MC, Ranchin B, Fabien N, Cochat P, Pouteil-Noble C, Trolliet P, Durieu I, Tebib J, Kassai B, Ansieau S, Puisieux A, Eliaou JF, Bonnefoy-Berard N (2009) Interleukin 17 acts in synergy with B cell-activating factor to influence B cell biology and the pathophysiology of systemic lupus erythematosus. Nat Immunol 10:778–785PubMedGoogle Scholar
  119. 119.
    Segal BM (2010) Th17 cells in autoimmune demyelinating disease. Semin Immunopathol 32:71–77PubMedGoogle Scholar
  120. 120.
    Piao WH, Jee YH, Liu RL, Coons SW, Kala M, Collins M, Young DA, Campagnolo DI, Vollmer TL, Bai XF, La Cava A, Shi FD (2008) IL-21 modulates CD4+CD25+ regulatory T-cell homeostasis in experimental autoimmune encephalomyelitis. Scand J Immunol 67:37–46PubMedGoogle Scholar
  121. 121.
    Spolski R, Kim HP, Zhu W, Levy DE, Leonard WJ (2009) IL-21 mediates suppressive effects via its induction of IL-10. J Immunol 182:2859–2867PubMedGoogle Scholar
  122. 122.
    Li MO, Flavell RA (2008) TGF-beta: a master of all T cell trades. Cell 134:392–404PubMedGoogle Scholar
  123. 123.
    Horwitz DA (2006) Transforming growth factor-beta: taking control of T cells’ life and death. Immunity 25:399–401PubMedGoogle Scholar
  124. 124.
    Li MO, Wan YY, Sanjabi S, Robertson AK, Flavell RA (2006) Transforming growth factor-beta regulation of immune responses. Annu Rev Immunol 24:99–146PubMedGoogle Scholar
  125. 125.
    Xiao BG, Zhu WH, Lu CZ (2007) The presence of GM-CSF and IL-4 interferes with effect of TGF-beta1 on antigen presenting cells in patients with multiple sclerosis and in rats with experimental autoimmune encephalomyelitis. Cell Immunol 249:30–36PubMedGoogle Scholar
  126. 126.
    Laouar Y, Town T, Jeng D, Tran E, Wan Y, Kuchroo VK, Flavell RA (2008) TGF-beta signaling in dendritic cells is a prerequisite for the control of autoimmune encephalomyelitis. Proc Natl Acad Sci USA 105:10865–10870PubMedGoogle Scholar
  127. 127.
    Lu LY, Chu JJ, Lu PJ, Sung PK, Hsu CM, Tseng JC (2008) Expression of intracellular transforming growth factor-beta1 in CD4+CD25+ cells in patients with systemic lupus erythematosus. J Microbiol Immunol Infect 41:165–173PubMedGoogle Scholar
  128. 128.
    Veldhoen M, Hocking RJ, Flavell RA, Stockinger B (2006) Signals mediated by transforming growth factor-beta initiate autoimmune encephalomyelitis, but chronic inflammation is needed to sustain disease. Nat Immunol 7:1151–1156PubMedGoogle Scholar
  129. 129.
    Manel N, Unutmaz D, Littman DR (2008) The differentiation of human T(H)-17 cells requires transforming growth factor-beta and induction of the nuclear receptor RORgammat. Nat Immunol 9:641–649PubMedGoogle Scholar
  130. 130.
    Yang L, Anderson DE, Baecher-Allan C, Hastings WD, Bettelli E, Oukka M, Kuchroo VK, Hafler DA (2008) IL-21 and TGF-beta are required for differentiation of human T(H)17 cells. Nature 454:350–352PubMedGoogle Scholar
  131. 131.
    Creange A, Belec L, Clair B, Degos JD, Raphael JC, Gherardi RK (1998) Circulating transforming growth factor beta 1 (TGF-beta1) in Guillain–Barre syndrome: decreased concentrations in the early course and increase with motor function. J Neurol Neurosurg Psychiatry 64:162–165PubMedGoogle Scholar
  132. 132.
    Ossege LM, Sindern E, Voss B, Malin JP (2000) Expression of TNFalpha and TGFbeta1 in Guillain–Barre syndrome: correlation of a low TNFalpha-/TGFbeta1-mRNA ratio with good recovery and signs for immunoregulation within the cerebrospinal fluid compartment. Eur J Neurol 7:17–25PubMedGoogle Scholar
  133. 133.
    Zhu J, Mix E, Olsson T, Link H (1994) Cellular mRNA expression of interferon-gamma, IL-4 and transforming growth factor-beta (TGF-beta) by rat mononuclear cells stimulated with peripheral nerve myelin antigens in experimental allergic neuritis. Clin Exp Immunol 98:306–312PubMedGoogle Scholar
  134. 134.
    Dahle C, Kvarnstrom M, Ekerfelt C, Samuelsson M, Ernerudh J (2003) Elevated number of cells secreting transforming growth factor beta in Guillain–Barre syndrome. APMIS 111:1095–1104PubMedGoogle Scholar
  135. 135.
    Sindern E, Schweppe K, Ossege LM, Malin JP (1996) Potential role of transforming growth factor-beta 1 in terminating the immune response in patients with Guillain–Barre syndrome. J Neurol 243:264–268PubMedGoogle Scholar
  136. 136.
    O’Garra A, Barrat FJ, Castro AG, Vicari A, Hawrylowicz C (2008) Strategies for use of IL-10 or its antagonists in human disease. Immunol Rev 223:114–131PubMedGoogle Scholar
  137. 137.
    Saraiva M, Christensen JR, Veldhoen M, Murphy TL, Murphy KM, O’Garra A (2009) Interleukin-10 production by Th1 cells requires interleukin-12-induced STAT4 transcription factor and ERK MAP kinase activation by high antigen dose. Immunity 31:209–219PubMedGoogle Scholar
  138. 138.
    Atkins S, Loescher AR, Boissonade FM, Smith KG, Occleston N, O’Kane S, Ferguson MW, Robinson PP (2007) Interleukin-10 reduces scarring and enhances regeneration at a site of sciatic nerve repair. J Peripher Nerv Syst 12:269–276PubMedGoogle Scholar
  139. 139.
    Milligan ED, Sloane EM, Watkins LR (2008) Glia in pathological pain: a role for fractalkine. J Neuroimmunol 198:113–120PubMedGoogle Scholar
  140. 140.
    Ledeboer A, Jekich BM, Sloane EM, Mahoney JH, Langer SJ, Milligan ED, Martin D, Maier SF, Johnson KW, Leinwand LA, Chavez RA, Watkins LR (2007) Intrathecal interleukin-10 gene therapy attenuates paclitaxel-induced mechanical allodynia and proinflammatory cytokine expression in dorsal root ganglia in rats. Brain Behav Immun 21:686–698PubMedGoogle Scholar
  141. 141.
    Stern JN, Keskin DB, Zhang H, Lv H, Kato Z, Strominger JL (2008) Amino acid copolymer-specific IL-10-secreting regulatory T cells that ameliorate autoimmune diseases in mice. Proc Natl Acad Sci USA 105:5172–5176PubMedGoogle Scholar
  142. 142.
    Myhr KM, Vagnes KS, Maroy TH, Aarseth JH, Nyland HI, Vedeler CA (2003) Interleukin-10 promoter polymorphisms in patients with Guillain–Barre syndrome. J Neuroimmunol 139:81–83PubMedGoogle Scholar
  143. 143.
    Yun W, Hua-bing W, Wei-zhi W (2007) A study of associated cell-mediated immune mechanisms in experimental autoimmune neuritis rats. J Neuroimmunol 185:87–94PubMedGoogle Scholar
  144. 144.
    Dahle C, Ekerfelt C, Vrethem M, Samuelsson M, Ernerudh J (1997) T helper type 2 like cytokine responses to peptides from P0 and P2 myelin proteins during the recovery phase of Guillain–Barre syndrome. J Neurol Sci 153:54–60PubMedGoogle Scholar
  145. 145.
    Oppenheim JJ, Zachariae CO, Mukaida N, Matsushima K (1991) Properties of the novel proinflammatory supergene “intercrine” cytokine family. Annu Rev Immunol 9:617–648PubMedGoogle Scholar
  146. 146.
    Ransohoff RM, Glabinski A, Tani M (1996) Chemokines in immune-mediated inflammation of the central nervous system. Cytokine Growth Factor Rev 7:35–46PubMedGoogle Scholar
  147. 147.
    Luster AD (1998) Chemokines–chemotactic cytokines that mediate inflammation. N Engl J Med 338:436–445PubMedGoogle Scholar
  148. 148.
    Zou LP, Pelidou SH, Abbas N, Deretzi G, Mix E, Schaltzbeerg M, Winblad B, Zhu J (1999) Dynamics of production of MIP-1alpha, MCP-1 and MIP-2 and potential role of neutralization of these chemokines in the regulation of immune responses during experimental autoimmune neuritis in Lewis rats. J Neuroimmunol 98:168–175PubMedGoogle Scholar
  149. 149.
    Orlikowski D, Chazaud B, Plonquet A, Poron F, Sharshar T, Maison P, Raphael JC, Gherardi RK, Creange A (2003) Monocyte chemoattractant protein 1 and chemokine receptor CCR2 productions in Guillain–Barre syndrome and experimental autoimmune neuritis. J Neuroimmunol 134:118–127PubMedGoogle Scholar
  150. 150.
    Kieseier BC, Tani M, Mahad D, Oka N, Ho T, Woodroofe N, Griffin JW, Toyka KV, Ransohoff RM, Hartung HP (2002) Chemokines and chemokine receptors in inflammatory demyelinating neuropathies: a central role for IP-10. Brain 125:823–834PubMedGoogle Scholar
  151. 151.
    Fujioka T, Kolson DL, Rostami AM (1999) Chemokines and peripheral nerve demyelination. J Neurovirol 5:27–31PubMedGoogle Scholar
  152. 152.
    Press R, Pashenkov M, Jin JP, Link H (2003) Aberrated levels of cerebrospinal fluid chemokines in Guillain–Barre syndrome and chronic inflammatory demyelinating polyradiculoneuropathy. J Clin Immunol 23:259–267PubMedGoogle Scholar
  153. 153.
    Luongo L, Sajic M, Grist J, Clark AK, Maione S, Malcangio M (2008) Spinal changes associated with mechanical hypersensitivity in a model of Guillain–Barre syndrome. Neurosci Lett 437:98–102PubMedGoogle Scholar
  154. 154.
    Chitnis T, Najafian N, Benou C, Salama AD, Grusby MJ, Sayegh MH, Khoury SJ (2001) Effect of targeted disruption of STAT4 and STAT6 on the induction of experimental autoimmune encephalomyelitis. J Clin Invest 108:739–747PubMedGoogle Scholar
  155. 155.
    Wurster AL, Tanaka T, Grusby MJ (2000) The biology of Stat4 and Stat6. Oncogene 19:2577–2584PubMedGoogle Scholar
  156. 156.
    Kaplan MH, Sun YL, Hoey T, Grusby MJ (1996) Impaired IL-12 responses and enhanced development of Th2 cells in Stat4-deficient mice. Nature 382:174–177PubMedGoogle Scholar
  157. 157.
    O’Sullivan LA, Liongue C, Lewis RS, Stephenson SE, Ward AC (2007) Cytokine receptor signaling through the Jak-Stat-Socs pathway in disease. Mol Immunol 44:2497–2506PubMedGoogle Scholar
  158. 158.
    Fujimoto M, Tsutsui H, Xinshou O, Tokumoto M, Watanabe D, Shima Y, Yoshimoto T, Hirakata H, Kawase I, Nakanishi K, Kishimoto T, Naka T (2004) Inadequate induction of suppressor of cytokine signaling-1 causes systemic autoimmune diseases. Int Immunol 16:303–314PubMedGoogle Scholar
  159. 159.
    Egan PJ, Lawlor KE, Alexander WS, Wicks IP (2003) Suppressor of cytokine signaling-1 regulates acute inflammatory arthritis and T cell activation. J Clin Invest 111:915–924PubMedGoogle Scholar
  160. 160.
    Malemud CJ, Miller AH (2008) Pro-inflammatory cytokine-induced SAPK/MAPK and JAK/STAT in rheumatoid arthritis and the new anti-depression drugs. Expert Opin Ther Targets 12:171–183PubMedGoogle Scholar
  161. 161.
    Roman-Blas JA, Jimenez SA (2008) Targeting NF-kappaB: a promising molecular therapy in inflammatory arthritis. Int Rev Immunol 27:351–374PubMedGoogle Scholar
  162. 162.
    Mangano K, Dati G, Quattrocchi C, Proietti L, Mazzarino C, Di Marco R, Bendtzen K, Greco B, Zaratin P, Nicoletti F (2008) Preventive and curative effects of cyclophosphamide in an animal model of Guillain–Barre syndrome. J Neuroimmunol 196:107–115PubMedGoogle Scholar
  163. 163.
    Brereton CF, Sutton CE, Lalor SJ, Lavelle EC, Mills KH (2009) Inhibition of ERK MAPK suppresses IL-23- and IL-1-driven IL-17 production and attenuates autoimmune disease. J Immunol 183:1715–1723PubMedGoogle Scholar
  164. 164.
    Wu T, Mohan C (2009) The AKT axis as a therapeutic target in autoimmune diseases. Endocr Metab Immune Disord Drug Targets 9:145–150PubMedGoogle Scholar
  165. 165.
    Peifer C, Wagner G, Laufer S (2006) New approaches to the treatment of inflammatory disorders small molecule inhibitors of p38 MAP kinase. Curr Top Med Chem 6:113–149PubMedGoogle Scholar
  166. 166.
    Ding C, Xu J, Li J (2008) ABT-874, a fully human monoclonal anti-IL-12/IL-23 antibody for the potential treatment of autoimmune diseases. Curr Opin Investig Drugs 9:515–522PubMedGoogle Scholar
  167. 167.
    Billich A (2007) Drug evaluation: apilimod, an oral IL-12/IL-23 inhibitor for the treatment of autoimmune diseases and common variable immunodeficiency. IDrugs 10:53–59PubMedGoogle Scholar
  168. 168.
    Wittig BM (2007) Drug evaluation: CNTO-1275, a mAb against IL-12/IL-23p40 for the potential treatment of inflammatory diseases. Curr Opin Investig Drugs 8:947–954PubMedGoogle Scholar
  169. 169.
    Badovinac VP, Tvinnereim AR, Harty JT (2000) Regulation of antigen-specific CD8+ T cell homeostasis by perforin and interferon-gamma. Science 290:1354–1358PubMedGoogle Scholar
  170. 170.
    Hassan AT, Dai Z, Konieczny BT, Ring GH, Baddoura FK, Abou-Dahab LH, El-Sayed AA, Lakkis FG (1999) Regulation of alloantigen-mediated T-cell proliferation by endogenous interferon-gamma: implications for long-term allograft acceptance. Transplantation 68:124–129PubMedGoogle Scholar
  171. 171.
    Skurkovich S, Boiko A, Beliaeva I, Buglak A, Alekseeva T, Smirnova N, Kulakova O, Tchechonin V, Gurova O, Deomina T, Favorova OO, Skurkovic B, Gusev E (2001) Randomized study of antibodies to IFN-gamma and TNF-alpha in secondary progressive multiple sclerosis. Mult Scler 7:277–284PubMedGoogle Scholar
  172. 172.
    Skurkovich B, Skurkovich S (2007) Autoimmune diseases are connected with disturbances in cytokine synthesis, and therapy with IFN-gamma blockers is their main pathogenetic treatment. Ann N Y Acad Sci 1109:167–177PubMedGoogle Scholar
  173. 173.
    Csurhes PA, Sullivan AA, Green K, Pender MP, McCombe PA (2005) T cell reactivity to P0, P2, PMP-22, and myelin basic protein in patients with Guillain–Barre syndrome and chronic inflammatory demyelinating polyradiculoneuropathy. J Neurol Neurosurg Psychiatry 76:1431–1439PubMedGoogle Scholar
  174. 174.
    Abbas N, Zou LP, Pelidou SH, Winblad B, Zhu J (2000) Protective effect of Rolipram in experimental autoimmune neuritis: protection is associated with down-regulation of IFN-gamma and inflammatory chemokines as well as up-regulation of IL-4 in peripheral nervous system. Autoimmunity 32:93–99PubMedGoogle Scholar
  175. 175.
    Zou LP, Deretzi G, Pelidou SH, Levi M, Wahren B, Quiding C, van der Meide P, Zhu J (2000) Rolipram suppresses experimental autoimmune neuritis and prevents relapses in Lewis rats. Neuropharmacology 39:324–333PubMedGoogle Scholar
  176. 176.
    Zou LP, Abbas N, Volkmann I, Nennesmo I, Levi M, Wahren B, Winblad B, Hedlund G, Zhu J (2002) Suppression of experimental autoimmune neuritis by ABR-215062 is associated with altered Th1/Th2 balance and inhibited migration of inflammatory cells into the peripheral nerve tissue. Neuropharmacology 42:731–739PubMedGoogle Scholar
  177. 177.
    Zhang Z, Zhang ZY, Fauser U, Schluesener HJ (2008) Valproic acid attenuates inflammation in experimental autoimmune neuritis. Cell Mol Life Sci 65:4055–4065PubMedGoogle Scholar
  178. 178.
    Zhang ZY, Zhang Z, Fauser U, Schluesener HJ (2009) Improved outcome of EAN, an animal model of GBS, through amelioration of peripheral and central inflammation by minocycline. J Cell Mol Med 13:341–351PubMedGoogle Scholar
  179. 179.
    Zhang Z, Zhang ZY, Schluesener HJ (2009) Compound A, a plant origin ligand of glucocorticoid receptors, increases regulatory T cells and M2 macrophages to attenuate experimental autoimmune neuritis with reduced side effects. J Immunol 183:3081–3091PubMedGoogle Scholar
  180. 180.
    Zhang ZY, Zhang Z, Schluesener HJ (2010) MS-275, an histone deacetylase inhibitor, reduces the inflammatory reaction in rat experimental autoimmune neuritis. Neuroscience 169(1):370–377PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Department of Neurology, The First HospitalJilin UniversityChangchunChina
  2. 2.Department of Neurology, The First HospitalDalian Medical UniversityDalianChina
  3. 3.Division of Neurodegeneration (NOVUM, plan 5), Department of Neurobiology, Care Sciences and Society, Karolinska InstituteKarolinska University Hospital in HuddingeStockholmSweden

Personalised recommendations