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Serum interleukin-18 and interleukin-10 levels in systemic lupus erythematosus: correlation with SLEDAI score and disease activity parameters

Abstract

Aim

The aim of the study was to assess serum levels of interleukin (IL)-18 and IL-10 in systemic lupus erythematosus (SLE) patients and their relationship with disease activity.

Patients and methods

Thirty patients with SLE and 20 healthy controls were investigated in this study. The serum IL-18 and IL-10 levels were determined using enzyme-linked immunosorbent assay and their correlations with the disease activity were measured using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and laboratory parameters, including erythrocyte sedimentation rate, anti-ds DNA antibody, complement 3, and complement 4 levels were analyzed.

Results

The serum IL-18 and serum IL-10 levels were significantly higher (mean values 1770.2 ± 360.4 and 842.65 ± 315.37 pg/ml for IL-18 and IL-10, respectively) in SLE patients compared with the controls (110.65 ± 30.37 vs. 76 ± 14.2 pg/ml, respectively, P < 0.001). The increase in serum levels of IL-18 and IL-10 directly and significantly correlated with each other (r = 0.404, P = 0.037). Furthermore, such an increase in the levels of these two cytokines showed a highly significant positive correlation with the SLEDAI scores and anti-ds DNA in the studied patients (P < 0.001).

Conclusion

The circulating IL-18 and IL-10 concentrations were significantly elevated in SLE patients and correlated with the SLEDAI score. The study emphasized that there exists an upregulated proinflammatory as well as anti-inflammatory responses in patients with active SLE; however, the anti-inflammatory response is not enough to suppress the active disease. Identifying the exact contribution of the currently studied cytokines might provide future insights for targeted therapeutic strategies in SLE.

References

  1. Manson JJ, Rahman A. Systemic lupus erythematosus. Orphanet J Rare Dis 2006; 1:6.

    PubMed  PubMed Central  Google Scholar 

  2. Lee HM, Sugino H, Nishimoto N. Cytokine networks in systemic lupus erythematosus. J Biomed Biotechnol 2010; 2010:676284.

    PubMed  PubMed Central  Google Scholar 

  3. Sekigawa I, Fujishiro M, Yamaguchi A, et al. A new hypothesis of the possible mechanisms of gender differences in systemic lupus erythematosus. Clin Exp Rheumatol 2010; 28:419-423.

    Google Scholar 

  4. Viallard J, Pellegrin J, Ranchin V, et al. 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; 115:189–195.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Pan HF, Ye DQ, Li XP. Type 17 T-helper cells might be a promising therapeutic target for systemic lupus erythematosus. Nat Clin Pract Rheumatol 2008; 4:352–353.

    CAS  PubMed  Google Scholar 

  6. Csiszar A, Nagy G, Gergely P, Pozsonyi T, Pocsik E. Increased interferon-gamma (IFN-γ), IL-10 and decreased IL-4 mRNA expression in peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus (SLE). Clin Exp Immunol 2000; 122:464–470.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Robak E, Robak T, Wozniacka A, Zak-Prelich M, Sysa-Jedrzejowska A, Stepien H. Proinflammatory interferon-gamma –inducing monokines (interleukin-12, interleukin-18, interleukin-15) –serum profile in patients with systemic lupus erythematosus. Eur Cytokine Netw 2002; 13:364–368.

    CAS  PubMed  Google Scholar 

  8. Fehniger TA, Shah MH, Turner MJ, et al. 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 1999; 162:4511–4520.

    CAS  PubMed  Google Scholar 

  9. Xu W -D, Pan H-F, Ye D-Q. Association of interleukin-18 and systemic lupus erythematosus. Rheumatol Int 2013; 33:3055–3057.

    CAS  PubMed  Google Scholar 

  10. Dao T, Ohashi K, Kayano T, Kurimoto M, Okamura H. Interferon-gamma-inducing factor, a novel cytokine, enhances Fas ligand-mediated cytotoxicity of murine T helper 1 cells. Cell Immunol 1996; 173:230–235.

    CAS  PubMed  Google Scholar 

  11. Wong CK, Ho CY, Li EK, Tam LS, Lam CW. Elevated production of interleukin-18 is associated with renal disease in patients with systemic lupus erythematosus. Clin Exp Immunol 2002; 130:345–351.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Tokano Y, Suzuki J, Amano H, Nozawa K, Morimoto S, Hashimoto H. Increased levels of interleukin-18 in patients with systemic lupus erythematosus: comment on the article by Shibatomi et al. Arthritis Rheum 2002;46:1410–1411. author reply 1411–1412.

  13. Rhodes KA, Andrew EM, Newton DJ, Tramonti D, Carding SR. A subset of IL-10-producing gammadelta T cells protect the liver from Listeria-elicited, CD8(+) T cell-mediated injury. Eur J Immunol 2008; 38:2274–2283.

    CAS  PubMed  Google Scholar 

  14. Yanaba K, Bouaziz JD, Matsushita T, Tsubata T, Tedder TF. The development and function of regulatory B cells expressing IL-10 (B10 cells) requires antigen receptor diversity and TLR signals. J Immunol 2009; 182:7459–7472.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Lacki JK, Leszczynski P, Kelemen J, Muller W, Mackiewicz SH. Cytokine concentration in serum of lupus erythematosus patients: the effect on acute phase response. J Med 1997; 28:99–107.

    CAS  PubMed  Google Scholar 

  16. Romagnani S. Biology of human TH1 and TH2 cells. J Clin Immunol 1995; 15:121–129.

    CAS  PubMed  Google Scholar 

  17. Joss A, Akdis M, Faith A, Blaser K, Akdis CA. IL-10 directly acts on T cells by specifically altering the CD28 co-stimulation pathway. Eur J Immunol 2000; 30:1683–1690.

    CAS  PubMed  Google Scholar 

  18. Schuetze N, Schoeneberger S, Mueller U, Freudenberg MA, Alber G, Straubinger RK. IL-12 family members: differential kinetics of their TLR4-mediated induction by Salmonella enteritidis and the impact of IL-10 in bone marrow-derived macrophages. Int Immunol 2005; 17:649–659.

    CAS  PubMed  Google Scholar 

  19. Yin Z, Bahtiyar G, Zhang N, et al. IL-10 regulates murine lupus. J Immunol 2002; 169:2148–2155.

    CAS  PubMed  Google Scholar 

  20. Lauwerys BR, Garot N, Renauld JC, Houssiau FA. Interleukin-10 blockade corrects impaired in vitro cellular immune responses of systemic lupus erythematosus patients. Arthritis Rheum 2000; 43:1976–1981.

    CAS  PubMed  Google Scholar 

  21. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40:1725.

    PubMed  Google Scholar 

  22. Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH. Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 1992; 35:630–640.

    CAS  Google Scholar 

  23. Deodhar SD. C-reactive protein: the best laboratory indicator available for monitoring disease activity. Cleve Clin J Med 1989; 56:126–130.

    CAS  PubMed  Google Scholar 

  24. Seidel A, Arolt V, Hunstiger M, Rink L, Behnisch A, Kirchner H. Cytokine production and serum proteins in depression. Scand J Immunol 1995; 41:534–538.

    CAS  PubMed  Google Scholar 

  25. Mohan C, Adams S, Stanik V, Datta SK. Nucleosome: a major immunogen for pathogenic autoantibody-inducing T cells of lupus. J Exp Med 1993; 177:1367–1381.

    CAS  PubMed  Google Scholar 

  26. Strand V. Lessons learned from clinical trials in SLE. Autoimmun Rev 2007; 6:209–214.

    CAS  PubMed  Google Scholar 

  27. Arason GJ, Steinsson K, Kolka R, Vikingsdottir T, D’Ambrogio MS, Valdimarsson H. Patients with systemic lupus erythematosus are deficient in complement-dependent prevention of immune precipitation. Rheumatology (Oxford) 2004; 43:783–789.

    CAS  Google Scholar 

  28. Sturfelt G, Truedsson L. Complement and its breakdown products in SLE. Rheumatology (Oxford) 2005; 44:1227–1232.

    CAS  Google Scholar 

  29. Gaipl US, Munoz LE, Grossmayer G, et al. Clearance deficiency and systemic lupus erythematosus (SLE). J Autoimmun 2007; 28:114-121.

    Google Scholar 

  30. Tyrrell-Price J, Lydyard PM, Isenberg DA. The effect of interleukin-10 and of interleukin-12 on the in vitro production of anti-double-stranded DNA antibodies from patients with systemic lupus erythematosus. Clin Exp Immunol 2001; 124:118–125.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Dinarello CA. IL-18: a TH1-inducing, proinflammatory cytokine and new member of the IL-1 family. J Allergy Clin Immunol 1999; 103:11–24.

    CAS  PubMed  Google Scholar 

  32. Park MC, Park YB, Lee SK. Elevated interleukin-18 levels correlated with disease activity in systemic lupus erythematosus. Clin Rheumatol 2004; 23:225–229.

    PubMed  Google Scholar 

  33. Esfandiari E, McInnes IB, Lindop G, et al. A proinflammatory role of IL-18 in the development of spontaneous autoimmune disease. J Immunol 2001; 167:5338–5347.

    CAS  PubMed  Google Scholar 

  34. Calvani N, Richards HB, Tucci M, Pannarale G, Silvestris F. Up-regulation of IL-18 and predominance of a Th1 immune response is a hallmark of lupus nephritis. Clin Exp Immunol 2004; 138:171–178.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Tucci M, Quatraro C, Lombardi L, Pellegrino C, Dammacco F, Silvestris F. Glomerular accumulation of plasmacytoid dendritic cells in active lupus nephritis: role of interleukin-18. Arthritis Rheum 2008; 58:251–262.

    CAS  PubMed  Google Scholar 

  36. Chen DY, Hsieh CW, Chen KS, Chen YM, Lin FJ, Lan JL. Association of interleukin-18 promoter polymorphisms with WHO pathological classes and serum IL-18 levels in Chinese patients with lupus nephritis. Lupus 2009; 18:29–37.

    CAS  PubMed  Google Scholar 

  37. 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; 9:589–593.

    CAS  PubMed  Google Scholar 

  38. Amerio P, Frezzolini A, Abeni D, et al. Increased IL-18 in patients with systemic lupus erythematosus: relations with Th-1, Th-2, pro-inflammatory cytokines and disease activity. IL-18 is a marker of disease activity but does not correlate with pro-inflammatory cytokines. Clin Exp Rheumatol 2002; 20:535–538.

    CAS  Google Scholar 

  39. Mohsen MA, Abdel Karim SA, Abbas TM, Amin M. Serum interleukin-18 levels in patients with systemic lupus erythematosus: relation with disease activity and lupus nephritis. Egypt Rheumatol 2013; 35:45–51.

    Google Scholar 

  40. Horwitz D, Stohl W, Gray J. T lymphocytes, natural killer cells, cytokines, and immune regulation. Dubois’ Lupus Erythematosus 1997; 151:155.

  41. Andoh T, Kishi H, Motoki K, Nakanishi K, Kuraishi Y, Muraguchi A. Protective effect of IL-18 on kainate- and IL-1 beta-induced cerebellar ataxia in mice. J Immunol 2008; 180:2322–2328.

    CAS  PubMed  Google Scholar 

  42. Novick D, Elbirt D, Miller G, Dinarello CA, Rubinstein M, Sthoeger ZM. High circulating levels of free interleukin-18 in patients with active SLE in the presence of elevated levels of interleukin-18 binding protein. J Autoimmun 2010; 34:121–126.

    CAS  PubMed  Google Scholar 

  43. Ishida H, Muchamuel T, Sakaguchi S, Andrade S, Menon S, Howard M. Continuous administration of anti-interleukin 10 antibodies delays onset of autoimmunity in NZB/W F1 mice. J Exp Med 1994; 179:305–310.

    CAS  PubMed  Google Scholar 

  44. 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; 4:393–395.

    CAS  PubMed  Google Scholar 

  45. Llorente L, Richaud-Patin Y, Garcia-Padilla C, et al. Clinical and biologic effects of anti-interleukin-10 monoclonal antibody administration in systemic lupus erythematosus. Arthritis Rheum 2000; 43:1790–1800.

    CAS  PubMed  Google Scholar 

  46. Chun HY, Chung JW, Kim HA, et al. Cytokine IL-6 and IL-10 as biomarkers in systemic lupus erythematosus. J Clin Immunol 2007; 27:461–466.

    CAS  PubMed  Google Scholar 

  47. El-Sayed M, Nofal E, Al Mokadem S, Al Makhzangy I, Gaballah H, Akl H. Correlative study of serum Th1/Th2 cytokines levels in patients with systemic lupus erythematosus with SLEDAI. Egypt Dermatol Online J 2008; 4:3–19.

    Google Scholar 

  48. 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; 16:283–288.

    CAS  PubMed  Google Scholar 

  49. Ling GS, Cook HT, Botto M, Lau YL, Huang FP. An essential protective role of IL-10 in the immunological mechanism underlying resistance vs. susceptibility to lupus induction by dendritic cells and dying cells. Rheumatology (Oxford) 2011; 50:1773–1784.

    CAS  Google Scholar 

  50. Zediak VP, Hunter CA. IL-10 fails to inhibit the production of IL-18 in response to inflammatory stimuli. Cytokine 2003; 21:84–90.

    CAS  PubMed  Google Scholar 

  51. Yasutomo K. Pathological lymphocyte activation by defective clearance of self-ligands in systemic lupus erythematosus. Rheumatology (Oxford) 2003; 42:214–222.

    CAS  Google Scholar 

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Correspondence to Hanan S. Mohmad Abozaid MD.

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El-Fetouh, S.A., Mohammed, R.H.A. & Abozaid, H.S.M. Serum interleukin-18 and interleukin-10 levels in systemic lupus erythematosus: correlation with SLEDAI score and disease activity parameters. Egypt Rheumatol Rehabil 41, 160–166 (2014). https://doi.org/10.4103/1110-161X.147358

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Keywords

  • interleukin-10
  • interleukin-18
  • systemic lupus erythematosus
  • Systemic Lupus Erythematosus Disease Activity Index