Skip to main content
Log in

Elevated interleukin-18 levels correlated with disease activity in systemic lupus erythematosus

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

The aim of this study was to determine the serum interleukin-18 (IL-18) levels in patients with systemic lupus erythematosus (SLE) and to assess their relationship with disease activity. Thirty-five patients with SLE and 35 age- and sex-matched controls were enrolled in this study. Paired serum samples were collected from all the patients with SLE, both at active stage before treatment and at the stable stage after treatment. The serum IL-18 levels were determined using ELISA and their correlations with the disease activity, measured using the SLE Disease Activity Index (SLEDAI) and laboratory parameters such as anti-dsDNA antibody, CH50, C3, C4, and circulating immune complex levels, were analyzed. The serum IL-18 levels in patients with SLE were significantly higher than those in the controls, particularly when the disease status was active (mean±SD: active stage, 721.23±360.15 pg/ml; inactive stage, 343.68±317.78 pg/ml; controls, 113.98±13.22 pg/ml, p<0.05). The IL-18 levels measured at the active stage before treatment correlated well with SLEDAI (r=0.41, p<0.05) and anti-dsDNA antibody titer (r=0.35, p<0.05). When we compared the changes of the IL-18 level and those of parameters reflecting the disease activity between the active stage and the stable stage of the disease, it was found that the changes in IL-18 level correlated well with the changes of SLEDAI score during the patient’s disease course (r=0.39, p<0.05). In conclusion, the serum IL-18 levels were elevated in patients with SLE, and these increased levels correlated well with SLE disease activity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

CIC:

Circulating immune complex

IFN:

Interferon

IL:

Interleukin

SLE:

Systemic lupus erythematosus

TNF:

Tumor necrosis factor

References

  1. Amital H, Shoenfeld Y (1999) Autoimmunity and autoimmune diseases such as systemic lupus erythematosus. In: Lahita RG (ed) Systemic lupus erythematosus. Academic Press, New York, pp 1–11

  2. Horwitz DA, Stohl W, Gray JD (1997) T lymphocytes, natural killer cells, cytokines, and immune regulation. In: Wallace DJ, Hahn BH (eds) Dubois’ lupus erythematosus. Williams & Wilkins, Baltimore, pp 155–194

  3. Spronk PE, Terberg EJ, Limburg PC, Kallenberg CGM (1992) Plasma concentration of IL-6 in systemic lupus erythematosus: an indicator of disease activity? Clin Exp Immunol 90:106-110

    CAS  PubMed  Google Scholar 

  4. Lee WK, Song CH, Park YB et al. (1998) Correlation of serum interleukin-8 with clinical activity in systemic lupus erythematosus. Korean J Med 54:770–777

    Google Scholar 

  5. Park YB, Lee SK, Kim DS, Lee J, Lee CH, Song CH (1998) Elevated IL-10 levels correlated with disease activity in systemic lupus erythematosus. Clin Exp Rheumatol 16:283–288

    CAS  PubMed  Google Scholar 

  6. Tokano Y, Morimoto S, Kaneko H (1999) Levels of IL-12 in the sera of patients with systemic lupus erythematosus-relation to Th1- and Th2-derived cytokines. Clin Exp Immunol 116:169–173

    Article  CAS  PubMed  Google Scholar 

  7. Davas FM, Tsirogianni A, Kappou I (1999) Serum IL-16, TNF-α, p55 srTNF-α, p75 srTNF-α, srIL-12α levels and disease activity in systemic lupus erythematosus. Clin Rheumatol 18:17–22

    Article  CAS  PubMed  Google Scholar 

  8. Al-Janadi M, Al-Balla S, Al-Dalaan A, Raziuddin S (1993) Cytokine profile in systemic lupus erythematosus, rheumatoid arthritis and other rheumatic disease. J Clin Immunol 13:58–67

    CAS  PubMed  Google Scholar 

  9. Dinarello CA (1999) IL-18: a Th1-inducing, proinflammatory cytokine and new member of the IL-1 family. J Allergy Clin Immunol 13: 11–24

    Google Scholar 

  10. Okamura H, Tsutsi H, Komatsu M, et al. (1995) Cloning of a new cytokine that induces IFN-γ production by T cells. Nature 378:88–91

    CAS  PubMed  Google Scholar 

  11. Kohno K, Kataoka T, Ohtsuki Y, et al. (1997) IFN-γ-inducing factor (IGIF) is a costimulatory factor on the activation of Th1 but not Th2 cells and exerts its effect independently of IL-12. J Immunol 158:1541–1550

    CAS  PubMed  Google Scholar 

  12. Biet F, Locht C, Kremer L (2002) Immunoregulatory functions of IL-18 and its role in defense against bacterial pathogens. J Mol Med 80:147–162

    Article  CAS  PubMed  Google Scholar 

  13. Gracie JA, Forsey RJ, Chan WL, Gilmer A (1999) A proinflammatory role for IL-18 in rheumatoid arthritis. J Clin Invest 104:1393–1401

    CAS  PubMed  Google Scholar 

  14. Monteleone G, Trapasso F, Parrello T (1999) Bioactive IL-18 expression is up-regulated in Crohn’s disease. J Immunol 163:143–147

    CAS  PubMed  Google Scholar 

  15. Yamano T, Higashi T, Nouso K, Nakatsukasa H (2000) Serum IFN-γ inducing factor/IL-18 levels in primary biliary cirrhosis. Clin Exp Immunol 122:227–231

    Article  CAS  PubMed  Google Scholar 

  16. Wong CK, Ho CY, Li EK, Lam CWK (2000) Elevation of proinflammatory cytokine and Th2 cytokine concentrations in patients with systemic lupus erythematosus. Lupus 9:589–593

    Article  CAS  PubMed  Google Scholar 

  17. Wong CK, Li EK, Ho CY, Lam CW (2000) Elevation of plasma interleukin-18 concentration is correlated with disease activity in systemic lupus erythematosus. Rheumatology 39:1078–1081

    Article  CAS  PubMed  Google Scholar 

  18. Amerio P, Frezzolini A, Abeni D, et al. (2002) Increased IL-18 in patients with systemic lupus erythematosus: Relations with Th-1, Th-2, proinflammatory cytokines and disease activity. Il-18 is a marker of disease activity but does not correlate with pro-inflammatory cytokines. Clin Exp Rheumatol 20:525–528

    PubMed  Google Scholar 

  19. Nilsson UR, Nilsson B (1984) Simplified assays of hemolytic activity of the classical and alternative complement pathways. J Immunol Methods 72:49–59

    Article  CAS  PubMed  Google Scholar 

  20. Singh VK, Tingle AJ (1982) Detection of circulating immune complexby a C1q-microplate ELISA system. J Immunol Meth 50:109-114

    Article  CAS  Google Scholar 

  21. Horwitz DA, Jacob C (1994) The cytokine network in the pathogenesis of systemic lupus erythematosus and possible therapeutic implications. Springer Semin Immunopathol 16:181–200

    CAS  PubMed  Google Scholar 

  22. Segal R, Bermas BL, Dayan M, Kalush F, Shearer GM, Mozes E (1997) Kinetics of cytokine production in experimental systemic lupus erythematosus: involvement of T helper cell 1/T helper cell 2-type cytokines in disease. J Immunol 158:3009–3016

    CAS  PubMed  Google Scholar 

  23. Feldmann F, Brennan FM, Mini RN (1996) Role of cytokines in rheumatoid arthritis. Annu Rev Immunol 14:397–440

    PubMed  Google Scholar 

  24. Rothe H, Jenkins NA, Copeland NG, Kolb H (1997) Active stage of autoimmune diabetes is associated with the expression of a novel cytokine, IGIF, which is located near Idd2. J Clin Invest 99:469–474

    CAS  PubMed  Google Scholar 

  25. Yoshimoto T, Takeda K, Tanaka T, et al. (1998) IL-12 up-regulates IL-18 receptor expression on T cells, Th1 cells, and B cells: synergism with IL-18 for IFN-gamma production. J Immunol 161:3400–3407

    CAS  PubMed  Google Scholar 

  26. Hoshino T, Wiltrout RH, Young HA (1999) IL-18 is a potent coinducer of IL-13 in NK and T cells: a new potential role for IL-18 in modulating the immune response. J Immunol 162:5070–5077

    CAS  PubMed  Google Scholar 

  27. Nakanishi K, Yoshimoto T, Tsutsui H, Okamura H (2001) Interleukin-18 regulates both Th1 and Th2 responses. Annu Rev Immunol 19:423–474

    CAS  PubMed  Google Scholar 

  28. Fehniger TA, Shah MH, Turner MJ, et al. (1999) Differential cytokine and chemokine gene expression by human NK cells following activation with IL-18 or IL-15 in combination with IL-12: implications for the innate immune response. J Immunol 162:4511–4520

    CAS  PubMed  Google Scholar 

  29. Dinarello CA (1997) Role of pro- and anti-iflammatory cytokines during inflammation: experimental and clinical findings. J Biol Regul Homeost Agents 11:91–103

    CAS  PubMed  Google Scholar 

  30. Tsutsui H, Matsui K, Kawada N, et al. (1997) IL-18 accounts for both TNF-alpha- and Fas ligand-mediated hepatotoxic pathways in endotoxin-induced liver injury in mice. J Immunol 159:3961–3967

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Soo Kon Lee.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Park, M., Park, Y. & Lee, S. Elevated interleukin-18 levels correlated with disease activity in systemic lupus erythematosus. Clin Rheumatol 23, 225–229 (2004). https://doi.org/10.1007/s10067-004-0867-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-004-0867-x

Keywords

Navigation