Journal of Clinical Immunology

, Volume 27, Issue 5, pp 461–466 | Cite as

Cytokine IL-6 and IL-10 as Biomarkers in Systemic Lupus Erythematosus

  • Hye-Young Chun
  • Jae-Wook Chung
  • Hyoun-Ah Kim
  • Jeong-Moon Yun
  • Ja-Young Jeon
  • Young-Min Ye
  • Seung-Hyun Kim
  • Hae-Sim Park
  • Chang-Hee Suh
Article

Abstract

There is a great deal of interest in the identification of biomarkers that are closely associated with disease activity in systemic lupus erythematosus (SLE), but few biomarkers have been validated. Cytokines play an important role in the pathogenesis of SLE. Therefore, we evaluated the levels of cytokines and their possible association with disease activity. In the present study, we found that the SLE patients had higher IL-6, IL-10, IL-12, and IFN-γ levels, but lower IL-2, than normal controls. Serum IL-6 level was significantly elevated in active SLE patients and correlated with the SLE activity index (SLEDAI), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Serum IL-10 level was also significantly elevated in active SLE patients and revealed positive correlation with SLEDAI and anti-double-stranded DNA (dsDNA) titer and negative correlation with C3, C4, and lymphocyte counts. No significant differences in the levels of cytokines were observed between SLE patients with nephritis and those without nephritis. These data suggest that IL-6 and IL-10 may be a useful biomarker for disease activity in SLE.

Keywords

Systemic lupus erythematosus biomarker cytokines 

Reference

  1. 1.
    Kotzin BL. Systemic lupus erythematosus. Cell 1996;85:303–6.PubMedCrossRefGoogle Scholar
  2. 2.
    Illei GG, Tackey E, Lapteva L, Lipsky PE. Biomarkers in systemic lupus erythematosus. I. General overview of biomarkers and their applicability. Arthritis Rheum 2004;50:1709–20.PubMedCrossRefGoogle Scholar
  3. 3.
    Illei GG, Tackey E, Lapteva L, Lipsky PE. Biomarkers in systemic lupus erythematosus. II. Markers of disease activity. Arthritis Rheum 2004;50:2048–65.PubMedCrossRefGoogle Scholar
  4. 4.
    Liu CC, Manzi S, Ahearn JM. Biomarkers for systemic lupus erythematosus: a review and perspective. Curr Opin Rheumatol 2005;17:543–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Liang MH, Socher SA, Larson MG, Schur PH. Reliability and validity of six systems for the clinical assessment of disease activity in systemic lupus erythematosus. Arthritis Rheum 1989;32:1107–18.PubMedCrossRefGoogle Scholar
  6. 6.
    Gillian SD, Jonathan TP, Esther C, David AI. Cytokines and systemic lupus erythematosus. Ann Rheum Dis 2000;59:243–51.CrossRefGoogle Scholar
  7. 7.
    Doria A, Ghirardello A, Iaccarino L, Zampieri S, Punzi L, Tarricone E, Ruffatti A, Sulli A, Sarzi-Puttini PC, Gambari PF, Cutolo M. Pregnancy, cytokines, and disease activity in systemic lupus erythematosus. Arthritis Rheum 2004;51:989–95.PubMedCrossRefGoogle Scholar
  8. 8.
    Romagnani S. The Th1/Th2 paradigm. Immunol Today 1997;18:263–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Ogawa N, Itoh M, Goto Y. Abnormal production of B cell growth factor in patients with systemic lupus erythematosus. Clin Exp Immunol 1992;89:26–31.PubMedCrossRefGoogle Scholar
  10. 10.
    Funauchi M, Ikoma S, Enomoto H, Horiuchi A. Decreased Th1-like and increased Th2-like cells in systemic lupus erythematosus. Scand J Rheumatol 1998;27:219–24.PubMedCrossRefGoogle Scholar
  11. 11.
    Tokano Y, Morimoto S, Kaneko H, Amano H, Nozawa K, Takasaki Y, Hashimoto H. Levels of IL-12 in the sera of patients with systemic lupus erythematosus (SLE)-relation to Th1- and Th2-derived cytokines. Clin Exp Immunol 1999;116:169–73.PubMedCrossRefGoogle Scholar
  12. 12.
    Takahashi S, Fossati L, Iwamoto M, Merino R, Motta R, Kobayakawa T: Imbalance towards Th1 predominance is associated with acceleration of lupus-like autoimmune syndrome in MRL mice. J Clin Invest 1996;97:1597–604.PubMedCrossRefGoogle Scholar
  13. 13.
    Akahoshi M, Nakashima H, Tanaka Y, Kohsaka T, Nagano S, Ohgami E, Arinobu Y, Yamaoka K, Niiro H, Shinozaki M, Hirakata H, Horiuchi T, Otsuka T, Niho Y. Th1/Th2 balance of peripheral T helper cells in systemic lupus erythematosus. Arthritis Rheum 1999;42:1644–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Wong CK, Ho CY, Li EK, Lam CW. Elevation of proinflammatory cytokine (IL-18, IL-17, IL-12) and Th2 cytokine (IL-4) concentrations in patients with systemic lupus erythematosus. Lupus 2000;9:589–93.PubMedCrossRefGoogle Scholar
  15. 15.
    Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982;25:1271–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31:315–24.PubMedCrossRefGoogle Scholar
  17. 17.
    van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 1984;27:361–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Suh CH, Jung YS, Park HC, Lee CH, Lee J, Song CH, Lee WK, Park YB, Lee SK. Risk factors for infection and role of C-reactive protein in Korean patients with systemic lupus erythematosus. Clin Exp Rheumatol 2001;19:191–4.PubMedGoogle Scholar
  19. 19.
    Linker-Israeli M, Deans RJ, Wallace DJ, Prehn J, Ozeri-Chen T, Kinenberg JR. Elevated levels of endogenous IL-6 in systemic lupus erythematosus: a putative role in pathogenesis. J Immunol 1991;147:117–23.PubMedGoogle Scholar
  20. 20.
    Nagafuchi H, Suzuki N, Mizushima Y, Sakane T. Constitutive expression of IL-6 receptors and their role in the excessive B cell function in patients with systemic lupus erythematosus. J Immunol 1993;151:6525–34.PubMedGoogle Scholar
  21. 21.
    Stuart RA, Littlewood AJ, Maddison PJ, Hall ND. Elevated serum interleukin-6 levels associated with active disease in systemic connective tissue disorders. Clin Exp Rheumatol 1995;13:17–22.PubMedGoogle Scholar
  22. 22.
    Spronk PE, ter Borg EJ, Limburg PC, Kallenberg CG. Plasma concentration of IL-6 in systemic lupus erythematosus; an indicator of disease activity? Clin Exp Immunol 1992;90:106–110.PubMedCrossRefGoogle Scholar
  23. 23.
    Rousset F, Garcia E, Defrance C, Peronne DH, Hsu R, Kastelein K, Moore KW, Banchereau J. IL-10 is a potent growth and differentiation factor for activated human B lymphocytes. Proc Natl Acad Sci USA 1992;89:1890–3.PubMedCrossRefGoogle Scholar
  24. 24.
    Llorente L, Richaud-Patin Y, Fior R, Alcocer-Varela J, Wijdenes J, Fourrier BM, Galanaud P, Emilie D. In vivo production of interleukin-10 by non-T cells in rheumatoid arthritis, Sjo¨ gren’s syndrome, and systemic lupus erythematosus: a potential mechanism of B lymphocyte hyperactivity and autoimmunity. Arthritis Rheum 1994;37:1647–55.PubMedCrossRefGoogle Scholar
  25. 25.
    Houssiau FA, Lefebvre C, Vanden Berghe M, Lambert M, Devogelaer JP, Renauld JC. Serum interleukin 10 titers in systemic lupus erythematosus reflect disease activity. Lupus 1995;4:393–5.PubMedGoogle Scholar
  26. 26.
    Park YB, Lee SK, Kim DS, Lee J, Lee Ch, Song CH. Elevated interleukin-10 levels correlated with disease activity in systemic lupus erythematosus. Clin Exp Rheumatol 1998;16:283–8.PubMedGoogle Scholar
  27. 27.
    Bertagnolli MM, Lin BY, Young D, Herrmann SH. IL-12 augments antigen-dependent proliferation of activated T lymphocytes. J Immunol 1991;149:3778–83.Google Scholar
  28. 28.
    Liu TF, Jones BM. Impaired production of IL-12 in systemic lupus erythematosus. I. Excessive production of IL-10 suppresses production of IL-12 by monocytes. Cytokine 1998;10:140–7.PubMedCrossRefGoogle Scholar
  29. 29.
    Viallard JF, Pellegrin JL, Ranchin V, Schaeverbeke T, Dehais J, Longy-Boursier M, Ragnaud JM, Leng B, Moreau JF. Th1 (IL-2, interferon-gamma (IFN-gamma)) and Th2 (IL-10, IL-4) cytokine production by peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus (SLE). Clin Exp Immunol 1999;115:189–95.PubMedCrossRefGoogle Scholar
  30. 30.
    Linker-Israeli M, Bakke AC, Kitridou RC, Gendler S, Gillis S, Horwitz DA. Production of interleukin 1 and interleukin 2 in patients with systemic lupus erythematosus (SLE). J Immunol 1983;136:2651–5.Google Scholar
  31. 31.
    Huang YP, Perrin LH, Miescher PA, Zubler RH. Correlation of T and B cell activities in vitro and serum IL-2 levels in systemic lupus erythematosus. J Immunol 1988;141:827–33PubMedGoogle Scholar
  32. 32.
    Aringer M, Smolen LS. Cytokine expression in lupus kidneys. Lupus 2005;14:13–8.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Hye-Young Chun
    • 1
  • Jae-Wook Chung
    • 1
  • Hyoun-Ah Kim
    • 1
  • Jeong-Moon Yun
    • 1
  • Ja-Young Jeon
    • 1
  • Young-Min Ye
    • 1
  • Seung-Hyun Kim
    • 1
  • Hae-Sim Park
    • 1
  • Chang-Hee Suh
    • 1
  1. 1.Department of Allergy and RheumatologyAjou University School of MedicineSuwonSouth Korea

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