Skip to main content

Advertisement

Log in

Association of increased serum IL-33 levels with clinical and laboratory characteristics of systemic lupus erythematosus in Chinese population

  • Original Article
  • Published:
Clinical and Experimental Medicine Aims and scope Submit manuscript

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by abnormal production of autoantibodies and proinflammatory cytokines. Although interleukin-33 (IL-33), a novel number of the IL-1 family, has been reported to have proinflammatory effects, the association of IL-33 with SLE has remained unknown. The aim of this study was to examine whether the serum IL-33 level is associated with SLE. A total of 70 patients with SLE were recruited. Sera from these patients were obtained at their visit and were compared to sera from 40 healthy controls or 28 patients with rheumatoid arthritis (RA) for IL-33 level. Furthermore, blood samples from patients with SLE were determined for various SLE-related laboratory variables, including blood routine, complements, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) and some autoantibodies. Serum IL-33 level was significantly increased in patients with SLE, compared with healthy controls, but was lower than that with RA. In patients with SLE, most clinical and laboratory characteristics did not correlate with serum IL-33 levels, with exceptions of thrombocytopenia, erythrocytopenia, anti-SSB antibody, ESR, CRP and IgA. By Spearman’s correlation coefficient, patients with SLE showed close correlation of IL-33 with ESR, CRP and IgA, and by multivariate logistic regressions, patients with SLE showed significantly independent association of IL-33 with thrombocytopenia, erythrocytopenia and anti-SSB antibody. Our results suggest that IL-33 may play a role in acute phase of SLE, but it was not associated with course of the disease. Moreover, IL-33 may exert biologic effects on erythrocytes and platelets or their precursors in SLE.

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.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Fairhurst AM, Wandstrat AE, Wakeland EK (2006) Systemic lupus erythematosus: multiple immunologic phenotypes in a complex genetic disease. Adv Immunol 92:1–69

    Article  PubMed  CAS  Google Scholar 

  2. Vyse TJ, Kotzin BL (1998) Genetic susceptibility to systemic lupus erythematosus. Ann Rev Immunol 16:261–292

    Article  CAS  Google Scholar 

  3. Tsokos GC, Kammer GM (2000) Molecular aberrations in human systemic lupus erythematosus. Mol Med Today 6:418–424

    Article  PubMed  CAS  Google Scholar 

  4. Rahman A, Isenberg DA (2008) Systemic lupus erythematosus. N Engl J Med 358:929–939

    Article  PubMed  CAS  Google Scholar 

  5. Su KY, Pisetsky DS (2009) The role of extracellular DNA in autoimmunity in SLE. Scand J Immunol 70:175–183

    Article  PubMed  CAS  Google Scholar 

  6. McAlindon T (2000) Update on the epidemiology of systemic lupus erythematosus: new spins on old ideas. Curr Opin Rheumatol 12:104–112

    Article  PubMed  CAS  Google Scholar 

  7. Novick D, Elbirt D, Miller G, Dinarello CA, Rubinstein M, Sthoeger ZM (2009) 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 (Epub ahead of print)

  8. Lood C, Gullstrand B, Truedsson L, Olin AI, Alm GV, Ronnblom L, Sturfelt G, Eloranta ML, Bengtsson AA (2009) C1q inhibits immune complex-induced interferon-αproduction in plasmacytoid dendritic cells: a novel link between C1q deficiency and systemic lupus erythematosus pathogenesis. Arthr Rheum 60(10):3081–3090

    Article  CAS  Google Scholar 

  9. Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, McClanahan TK, Zurawski G, Moshrefi M, Qin J, Li X, Gorman DM, Bazan JF, Kastelein RA (2005) IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity 23:479–490

    Article  PubMed  CAS  Google Scholar 

  10. Brint EK, Fitzgerald KA, Smith P, Colye AJ, Gutierrez-Ramos JC, Fallon PG, O’Neil LA (2002) Characterization of signaling pathways activated by the interleukin 1(IL-1) receptor homologue T1/ST2. A role for Jun N-terminal kinase in IL-4 induction. J Biol Chem 277:49205–49211

    Article  PubMed  CAS  Google Scholar 

  11. Carriere V, Roussel L, Ortega N, Lacorre DA, Americh L, Aguilar L, Bouche G, Girard JP (2007) IL-33, the IL-1-like cytokine ligand for ST2 receptor, is a chromatin-associated nuclear factor in vivo. Proc Natl Acad Sci USA 104:282–287

    Article  PubMed  CAS  Google Scholar 

  12. Palmer G, Talabot-Ayer D, Lamacchia C, Toy D, Seemayer CA, Viatte S, Finckh A, Smith DE, Gabay C (2009) Inhibition of interleukin-33 signaling attenuateds the severity of expreimental arthritis. Arthr Rheum 60(3):738–749

    Article  CAS  Google Scholar 

  13. Gabay C, Mclnnes LB (2009) The biological and clinical importance of the ‘new generation’ cytokines in rheumatic diseases. Arthr Res Therapy 11:230–243

    Article  Google Scholar 

  14. Xu D, Jiang HR, Kewin P, Li Y, Mu R, Fraser AR, Pitman N, Kurowska-Stolarska M, McKenzie AN, Mclnnes IB, Liew FY (2008) IL-33 excacerbates antigen-incduced arthritis by activating mast cells. Proc Natl Acad Sci USA 105:10913–10918

    Article  PubMed  CAS  Google Scholar 

  15. Miller AM, Xu D, Asquith DL, Denby L, Li Y, Sattar N, Baker AH, Mclnnes IB, Liew FY (2008) IL-33 reduces the development of atherosclerosis. J Exp Med 205:339–346

    Article  PubMed  CAS  Google Scholar 

  16. Smithgall MD, Comeau MR, Yoon BR, Kaufman D, Armitage R, Smith DE (2008) IL-33 amplifies both Th1- and Th2-type responses through its activity on human basophils, allergen-reactive Th2 cells, iNKT and NK cells. Int Immunol 20(8):1019–1030

    Article  PubMed  CAS  Google Scholar 

  17. Morimoto S, Tokano YK, Kaneko H, Nozawa K, Amano H, Hashimoto H (2001) The increased interleukin-13 in patients with systemic lupus erythematosus: relation to other Th1-, Th2-related cytokines and clinical findings. Autoimmunity 34(1):19–25

    Article  PubMed  CAS  Google Scholar 

  18. Wen X, Zhang D, Kikuchi Y, Jiang Y, Nakamura K, Xiu Y, Tsurui H, Takahashi K, Abe M, Ohtsuji M, Nishimura H, Takatsu K, Shirai T, Hirose S (2004) Transgene-mediated hyper-expression of IL-5 inhibits autoimmune disease but increases the risk of B cell chronic lymphocytic leukemia in a model of murine lupus. Eur J Immunol 34(10):2740–2749

    Article  PubMed  CAS  Google Scholar 

  19. Gomez D, Correa PA, Gomez LM, Cadena J, Molina JF, Anaya JM (2004) Th1/Th2 cytokines in patients with systemic lupus erythematosus: is tumor necrosis factor a protective? Semin Arthr Rheum 33(6):404–413

    Article  CAS  Google Scholar 

  20. Pascual V, Allantaz F, Patel P, Palucka AK, Chaussabel D, Banchereau J (2008) How the sutdy of children with rheumatic diseases identified interferon-alpha and interliukin-1 as novel therapeutic targets. Immunol Rev 223:39–59

    Article  PubMed  CAS  Google Scholar 

  21. Aringer M, Smolen JS (2004) Tumour necrosis factor and other proinflammatory cytokines in systemic lupus erythematosus: a rationale for therapeutic intervention. Lupus 13(5):344–347

    Article  PubMed  CAS  Google Scholar 

  22. Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus [letter]. Arthr Rheum 40:1725

    Article  CAS  Google Scholar 

  23. Renal Disease Subcommittee of the American College of Rheumatology Ad Hoc Committee on Systemic Lupus Erythematosus Response Criteria (2006) The American College of Rheumatology response criteria for proliferative and membranous renal disease in systemic lupus erythematosus clinical trials. Arthr Rheum 54:421–432

    Article  Google Scholar 

  24. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS et al (1988) The American Rheumatism Assocaition 1987 revised criteria for the classification of rheumatoid arthritis. Arthr Rhuem 31:315–324

    Article  CAS  Google Scholar 

  25. Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang DH, the Committee on Prognosis Studies in SLE (1992) Derivation of the SLEDAI: a disease activity index for lupus patients. Arthr Rheum 35:630–640

    Article  CAS  Google Scholar 

  26. Mok MY, Huang FP, Ip WK, Lo Y, Wong FY, Chan EY, Lam KF, Xu D (2010) Serum levels of IL-33 and soluble ST2 and their association with disease activity in systemic lupus erythematosus. Rheumatology (Oxford) 49:520–527 [Epub ahead of print]

    Article  CAS  Google Scholar 

  27. McCarty DJ, Manzi S, Medsger TA Jr, Ramsey-Goldman R, LaPorte RE, Kwoh CK (1995) Incidence of systemic lupus erythematosus. Race and gender differences. Arthr Rheum 38:1260–1270

    Article  CAS  Google Scholar 

  28. Studenski S, Allen NB, Caldwell DS, Rice JR, Polisson RP (1987) Survival in systemic lupus erythematosus. A multivariate analysis of demographic factors. Arthr Rheum 30:1326–1332

    Article  CAS  Google Scholar 

  29. Bematsky S, Boivin JF, Joseph L et al (2006) Mortality in systemic lupus erythematosus. Arthr Rheum 54:2550–2557

    Article  Google Scholar 

  30. Rhew EY, Manzi SM, Dyer AR et al (2009) Differences in subclinical cardiovascular disease between African American and Caucasion women with systemic lupus erythematosus. Transl Res 153:51–59

    Article  PubMed  Google Scholar 

  31. Pecaric-Petkovic T, Didichenko SA, Kaempfer S, Spiegl N, Dahinden CA (2009) Human basophils and eosinophils are the direct target leukocytes of the novel IL-1 family member IL-33. Blood 113(7):1526–1534

    Article  PubMed  CAS  Google Scholar 

  32. Allakhverdi Z, Smith DE, Comeau MR, Delespesse G (2007) Cutting edge: The ST2 ligand IL-33 potently activates and drives maturation of human mast cells. J Immunol 179:2051–2054

    PubMed  CAS  Google Scholar 

  33. Iikura M, Suto H, Kajiwara N et al (2007) IL-33 can promote survival, adhesion and cytokine production in human mast cells. Lab Invest 87:971–978

    Article  PubMed  CAS  Google Scholar 

  34. Chung SA, Tian C, Taylor KE, Lee AT, Ortmann WA, Hom G, Graham RR, Nititham J, Kelly JA, Morrisey J, Wu H, Yin H, Alarcon-Riquelme ME, Tsao BP, Harley JB, Gaffney PM, Moser KL, Manzi S, Petri M, Gregersen PK, Langefeld CD, Behrens TW, Seldin MF, Criswell LA (2009) European population substructure is associated with mucocutaneous manifestations and autoantibody production in systemic lupus erythematosus. Arthr Rheum 60(8):2448–2456

    Article  Google Scholar 

  35. Samarkos M, Davies KA, Gordon C, Loizou S (2006) Clinical significance of IgA anticardiolipin and anti-β2-GP1 antibodies in patients with systemic lupus erythematosus and primary antiphosphlipid syndrome. Clin Rheumatol 25:199–204

    Article  PubMed  CAS  Google Scholar 

  36. Chen C, Lin K, Lin S, Tsai W, Yen J, Chang S, Lu S, Liu H (2005) High prevalence of immunoglobulin A antibody against Epstein-Barr virus capsid antigen in adult patients with lupus with disease flare: case control studies. J Rheumatol 32:44–47

    PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by a grant from the China National Natural Science Foundation Council (81001333).

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Renqian Zhong.

Additional information

Z. Yang and Y. Liang contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yang, Z., Liang, Y., Xi, W. et al. Association of increased serum IL-33 levels with clinical and laboratory characteristics of systemic lupus erythematosus in Chinese population. Clin Exp Med 11, 75–80 (2011). https://doi.org/10.1007/s10238-010-0115-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10238-010-0115-4

Keywords

Navigation