Journal of Neurology

, 258:1865

Elevated serum level of interleukin-32α in the patients with myasthenia gravis

  • Sang-Jun Na
  • Seon-Hwa So
  • Kee Ook Lee
  • Young-Chul Choi
Original Communication

Abstract

A new cytokine, interleukin-32 (IL-32), has been implicated in the pro-inflammatory immune responses in several autoimmune disorders, such as rheumatoid arthritis and inflammatory bowel diseases. Myasthenia gravis (MG) is a well-characterized autoimmune disease directed at the postsynaptic acetylcholine receptor (AChR) or end plate of the neuromuscular junction. IL-32 is a cytokine that induces tumor necrosis factor (TNF)-α, IL-6, IL-1β, and chemokine. IL-6, TNF-α, and IL-2 are related to the pathogenesis and immunoregulation of MG. The gene expression of IL-32 is increased in human natural killer (NK) cells and T lymphocytes when stimulated by IL-2 or mitogen. NK cells influence the development of experimental autoimmune MG (EAMG) and possibly MG. The aim of this study was to examine whether IL-32α levels are increased in patients with MG and to investigate the relationship between IL-32α levels and disease activity in human MG. Serum IL-32α levels were significantly higher in the MG patients (p = 0.03): 460.07 ± 192.30 pg/mL in MG patients and 248.45 ± 188.42 pg/mL in the healthy control group. Although there was no significant statistical difference, serum IL-32α levels of patients with both anti-AChR binding and blocking antibodies trended to be higher than those without either antibodies (521.56 ± 212.92 pg/mL vs. 339.52 ± 182.78 pg/mL, p = 0.16). IL-32α serum levels tended to decrease with clinical improvement in generalized MG. This study suggests the possibility that IL-32 might contribute to MG pathogenesis or immunoregulation.

Keywords

Interleukin-32α (IL-32α) Autoimmune disorder Myasthenia gravis (MG) Natural killer cell (NK) 

References

  1. 1.
    Shi FD, Wang HB, Li H, Hong S, Taniguchi M, Link H, Van Kaer L, Ljunggren HG (2000) Natural killer cells determine the outcome of B cell-mediated autoimmunity. Nat Immunol 1:245–251PubMedCrossRefGoogle Scholar
  2. 2.
    Conti-Fine BM, Milani M, Kaminski HJ (2006) Myasthenia gravis: past, present and future. J Clin Invest 116:2843–2854PubMedCrossRefGoogle Scholar
  3. 3.
    Dahl CA, Schall RP, He HL, Cairns JS (1992) Identification of a novel gene expressed inactivated natural killer cells and T cells. J Immunol 148:597–603PubMedGoogle Scholar
  4. 4.
    Kim SH, Han SY, Azam T, Yoon DY, Dinarello CA (2005) Interleukin-32: a cytokine and inducer of TNF alpha. Immunity 22:131–142PubMedGoogle Scholar
  5. 5.
    Dinarello CA, Kim SH (2006) IL-32, a novel cytokine with a possible role in disease. Ann Rheum Dis 65(Suppl 3):iii61–iii64PubMedCrossRefGoogle Scholar
  6. 6.
    Nold MF, Nold-Petry CA, Pott GB, Zepp JA, Saavedra MT, Kim SH, Dinarello CA (2008) Endogenous IL-32 controls cytokine and HIV-1 production. J Immunol 181:557–565PubMedGoogle Scholar
  7. 7.
    Joosten LA, Netea MG, Kim SH, Yoon DY, Oppers-Walgreen B, Radstake TR, Barrera P, van de Loo FA, Dinarello CA, van den Berg WB (2006) IL-32, a proinflammatory cytokine in rheumatoid arthritis. Proc Natl Acad Sci USA 103:3298–3303PubMedCrossRefGoogle Scholar
  8. 8.
    Shioya M, Nishida A, Yagi Y, Ogawa A, Tsujikawa T, Kim-Mitsuyama S, Takayanagi A, Shimizu N, Fujiyama Y, Andoh A (2007) Epithelial overexpression of interleukin-32alpha in inflammatory bowel disease. Clin Exp Immunol 149:480–486PubMedCrossRefGoogle Scholar
  9. 9.
    Jaretzki A 3rd, Barohn RJ, Ernstoff RM, Kaminski HJ, Keesey JC, Penn AS, Sanders DB (2000) Myasthenia gravis: recommendations for clinical research standards. Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America. Neurology 55:16–23PubMedGoogle Scholar
  10. 10.
    Drachman DB (1994) Myasthenia gravis. N Engl J Med 330:1797–1810PubMedCrossRefGoogle Scholar
  11. 11.
    Conti P, Youinou P, Theoharides TC (2007) Modulation of autoimmunity by the latest interleukins (with special emphasis on IL-32). Autoimmun Rev 6:131–137PubMedCrossRefGoogle Scholar
  12. 12.
    Netea MG, Azam T, Ferwerda G, Girardin SE, Walsh M, Park JS, Abraham E, Kim JM, Yoon DY, Dinarello CA, Kim SH (2005) IL-32 synergizes with nucleotide oligomerization domain (NOD) 1 and NOD2 ligands for IL-1beta and IL-6 production through a caspase 1-dependent mechanism. Proc Natl Acad Sci USA 102:16309–16314PubMedCrossRefGoogle Scholar
  13. 13.
    Jander S, Stoll G (2002) Increased serum levels of the interferon-gamma-inducing cytokine interleukin-18 in myasthenia gravis. Neurology 59:287–289PubMedGoogle Scholar
  14. 14.
    Furlan R, Martino G, Galbiati F, Poliani PL, Smiroldo S, Bergami A, Desina G, Comi G, Flavell R, Su MS, Adorini L (1999) Caspase-1 regulates the inflammatory process leading to autoimmune demyelination. J Immunol 163:2403–2409PubMedGoogle Scholar
  15. 15.
    Firestein GS (2003) Evolving concepts of rheumatoid arthritis. Nature 423:356–361PubMedCrossRefGoogle Scholar
  16. 16.
    van Dullemen HM, van Deventer SJ, Hommes DW, Bijl HA, Jansen J, Tytgat GN, Woody J (1995) Treatment of Crohn’s disease with anti-tumor necrosis factor chimeric monoclonal antibody (cA2). Gastroenterology 109:129–135PubMedCrossRefGoogle Scholar
  17. 17.
    Leonardi CL, Powers JL, Matheson RT, Goffe BS, Zitnik R, Wang A, Gottlieb AB, Etanercept Psoriasis Study Group (2003) Etanercept as monotherapy in patients with psoriasis. N Engl J Med 349:2014–2022PubMedCrossRefGoogle Scholar
  18. 18.
    Duan RS, Wang HB, Yang JS, Scallon B, Link H, Xiao BG (2002) Anti-TNF-alpha antibodies suppress the development of experimental autoimmune myasthenia gravis. J Autoimmun 19:169–174PubMedCrossRefGoogle Scholar
  19. 19.
    Deng C, Goluszko E, Tüzün E, Yang H, Christadoss P (2002) Resistance to experimental autoimmune myasthenia gravis in IL-6-deficient mice is associated with reduced germinal center formation and C3 production. J Immunol 169:1077–1083PubMedGoogle Scholar
  20. 20.
    Jelinek DF, Lipsky PE (1987) Enhancement of human B cell proliferation and differentiation by tumor necrosis factor-alpha and interleukin 1. J Immunol 139:2970–2976PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Sang-Jun Na
    • 1
    • 2
  • Seon-Hwa So
    • 1
  • Kee Ook Lee
    • 1
    • 2
  • Young-Chul Choi
    • 1
  1. 1.Department of Neurology, Gangnam Severance Hospital, Brain Korea 21 Project for Medical ScienceYonsei University College of MedicineSeoulRepublic of Korea
  2. 2.Department of NeurologyKonyang University College of MedicineDaejeonRepublic of Korea

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