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Cytokine inhibitors: soluble tumor necrosis factor receptor 1 and interleukin-1 receptor antagonist in Behçet’s disease

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Abstract

Serum levels of proinflammatory cytokines, interleukin-1 beta (IL-1β), tumor necrosis factor alpha, (TNF-α), and their inhibitors, IL-1 receptor antagonist (IL-1ra) and soluble TNF receptor 1 (sTNFR1), were determined by enzyme-linked immunosorbent assay in 104 patients with Behçet’s disease (65 active, 39 inactive) and 40 healthy controls. The levels of IL-1β and IL-1ra were significantly higher in both active and inactive patients than in control subjects (P<0.01 and P< 0.01, respectively). The concentrations of TNF-α and sTNFR1 were found to be higher in active patients than in controls (P< 0.01 and P< 0.001, respectively). There were no significant differences in the serum levels of these cytokines and their inhibitors between active and inactive patients. Significant increases in mean C-reactive protein level and erythrocyte sedimentation rate were found in patients with active vs inactive disease (P< 0.001 and P< 0.05, respectively). C-reactive protein values correlated with erythrocyte sedimentation rate but not with cytokines or their inhibitors. Our conclusion is that elevated serum TNF-α and sTNFR1 seem to be important inflammatory mediators in Behçet’s disease. The statistically significant increase in these levels may arise from the severity of inflammation in the tissue or organ involved.

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References

  1. Behçet H (1937) Über rezidivierende Aphthose, durch ein Virus verursachte Geschwüre am Mund, am Auge und an den Genitalien. Dermatol Wochenschr 36:1152–1157

    Google Scholar 

  2. O’Duffy JD (1994) Behçet’s disease. Curr Opin Rheumatol 6:39–43

    CAS  PubMed  Google Scholar 

  3. Brockhaus M, Shonfeld HJ, Schlaeger EJ, Hunziker W, Lesslauer W, Loetscher H (1990) Identification of two types of tumor necrosis factor receptors on human cell lines monoclonal antibodies. Proc Natl Acad Sci U S A 87:3127–3131

    CAS  PubMed  Google Scholar 

  4. Arend WP (2002) The mode of action of cytokine inhibitors. J Rheumatol 29 [Suppl 65]:16–21

    Google Scholar 

  5. Arend WP (1993) Interleukin-1 receptor antagonist. Adv Immunol 54:167–227

    CAS  PubMed  Google Scholar 

  6. Firestein GS, Boyle DL, Yu C, Paine MM, Whisenand TD, Zvaifler NJ, Arend WP (1994) Synovial interleukin-1 receptor antagonist and interleukin-1 balance in rheumatoid arthritis. Arthritis Rheum 37:644–652

    CAS  PubMed  Google Scholar 

  7. Cope AP, Aderka D, Doherty M, Engelmann H, Gibbons D, Jones AC et al (1992) Increased levels of soluble tumor necrosis factor receptors in the sera and synovial fluid of patients with rheumatic diseases. Arthritis Rheum 35:1160–1169

    CAS  PubMed  Google Scholar 

  8. Aderka D, Wysenbeek A, Engelman H, Cop AP, Brenanan F, Molad Y, Hornik V, Levo Y, Maini RN, Feldmann M et al (1993) Correlation between serum levels of soluble tumor necrosis factor receptor and disease activity in systemic lupus erythematosus. Arthritis Rheum 36:1111–1120

    CAS  PubMed  Google Scholar 

  9. Rooney M, Varsani H, Martin K, Lombard PR, Dayer JM, Woo P (2000) Tumor necrosis factor alpha and its soluble receptors in juvenile chronic arthritis. Rheumatology (Oxford) 39:432–438

    Google Scholar 

  10. Nasonov EL, Chichasanova NV, Samsanova MIU, Tilz GP, Niki Foravo EL, Stepanets OV, Nasonova MB, Fuks D (2001) Soluble receptors of TNF-alpha in rheumatoid arthritis. Klin Med (Mosck) 79:33–36

    Google Scholar 

  11. Suzuki Y, Takemura H, Kashiwagi H (1995) Interleukin-1 receptor antagonist in patients with active systemic lupus erythematosus. Enhanced production by monocytes and correlation with disease activity. Arthritis Rheum 38:1055–1059

    CAS  PubMed  Google Scholar 

  12. Gabay C, Gay Croisier F, Roux Lombard P et al (1994) Elevated serum levels of interleukin-1 receptor antagonist in polymyositis/dermatomyositis. A biologic marker of disease activity with a possible role in the lack of acute-phase protein response. Arthritis Rheum 37:1744–1751

    CAS  PubMed  Google Scholar 

  13. Yosipovitch YG, Shohat B, Bshara J, Wysenbeek A, Weinberger A (1995) Elevated serum interleukin-2 receptors and interleukin-Iβ in patients with Behçet’s disease: correlations with disease activity and severity. Isr J Med Sci 31:345–348

    CAS  PubMed  Google Scholar 

  14. Turan B, Galati H, Erdi H, Gürler A, Michel BA, Villiger PM (1997) Systemic levels of T cell regulatory cytokines IL-10 and IL-12 in Behçet’s disease: soluble TNFR-75 as a biological marker of disease activity. J Rheumatol 24:128–132

    CAS  PubMed  Google Scholar 

  15. International Study Group for Behçet’s Disease (1990) Criteria for diagnosis of Behçet’s disease. Lancet 335:1078–1080

    PubMed  Google Scholar 

  16. Dinarello CA (1995) Interleukin-1 and interleukin-1 receptor antagonist. Nutrition 11 [Suppl 5]:492–494

  17. 17 Yamashita N, Kaneoka H, Kaneko S et al (1997) Role of gammadelta T lymphocytes in the development of Behçet’s disease. Clin Exp Immunol 107:241–247

    CAS  PubMed  Google Scholar 

  18. Freysdotter J, Lau S, Fortune F (1999) Gamma-delta T cells in Behçet’s disease (BD) and recurrent aphthous stomatitis (RAS). Clin Exp Immunol 1118:451–457

    Article  Google Scholar 

  19. Sayinalp N, Özcebe OI, Özdemir O, Haznedaroğlu IC, Dündar S, Kirazli S (1996) Cytokines in Behçet’s disease. J Rheumatol 23:321–322

    CAS  PubMed  Google Scholar 

  20. Akoğlu TF, Direskeneli H, Yazıcı H, Lawrence R (1990) TNF, soluble IL-2R and soluble CD-8 in Behçet’s disease [letter]. J Rheumatol 17:1107–1113

    CAS  PubMed  Google Scholar 

  21. Evreklioğlu C, Er H, Turkoz Y, Cekmen M (2002) Serum levels of TNF-α, sIL-2R, IL-6 and IL-8 are increased and associated with elevated lipid peroxidation in patients with Behçet’s disease. Mediators Inflamm 11:87–93

    Article  PubMed  Google Scholar 

  22. Hamzaoui K, Hamza M, Ayed K (1990) Production of TNF-α and IL-1 in active Behçet’s disease. J Rheumatol 17:1428–1429

    CAS  PubMed  Google Scholar 

  23. MegeJL, Dilsen N, Sanguedolce V et al (1993) Overproduction of monocyte-derived tumor necrosis factor alpha, interleukin (IL)-6, IL-8 and increased neutrophil superoxide generation in Behçet’s disease. A comparative study with familial Mediterranean fever and healthy subjects. J Rheumatol 20:1544–1549

    CAS  PubMed  Google Scholar 

  24. Kurhan-Yavuz S, Direskeneli H, Bozkurt N et al (2000) Anti-MHC autoimmunity in Behçet’s disease: T cell responses to an HLA-B-derived peptide cross-reactive with retinal-S antigen in patients with uveitis. Clin Exp Immunol 120:162–166

    Article  CAS  PubMed  Google Scholar 

  25. Molvig J, Baek J, Christensen P, Manogue KR, Vlassara H, Platz P et al (1988) Endotoxin-stimulated human monocyte secretion of interleukin-1, tumor necrosis factor alpha and prostoglandin E2 shows stable inter-individual differences. Scand J Immunol 27:705–716

    CAS  PubMed  Google Scholar 

  26. Arend WP (2002) The mode of action of cytokine inhibitors. J Rheumatol 29 [Suppl 65]:16–21

    Google Scholar 

  27. Peschon JJ, Torrance DS, Stocking KL, Glaccum MB, Otten C, Willis CR (1998) TNF receptor deficient mice reveal divergent roles for p55 and p75 in several models of inflammation. J Immunol 160:943–952

    CAS  PubMed  Google Scholar 

  28. Bresnihan B, Cunnane G (1998) Interleukin-1 receptor antogonist. Rheumatol Dis Clin North Am 24:615

    CAS  Google Scholar 

  29. Aydıntuğ AO, Tokgöz G, Özoran K, Düzgün N, Gürler A, Tutkak H (1995) Elevated levels of soluble intercellular adhesion molecule-1 correlate with disease activity in Behçet’s disease. Rheumatol Int 15:75–78

    PubMed  Google Scholar 

  30. Memişoğlu H, Aksu HSZ, Erken E, Göcük M (1991) Serum interleukin-1 level in Behçet’s disease. In: O’Duffy JD, Kökmen E (eds) Behçet’s disease. Dekker, New York, pp 387–391

  31. Treudler R, Ketteler R, Orfanos CE, Zouboulis CC (1997) Increased serum levels of interleukin I-beta and basic fibroblast growth factor in severe Adamandiades-Behçet’s disease. In: Hamzaou M (ed) Behçet’s disease. Tunis, pp 33–37

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Correspondence to Nurşen Düzgün.

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Düzgün, N., Ayaşlioğlu, E., Tutkak, H. et al. Cytokine inhibitors: soluble tumor necrosis factor receptor 1 and interleukin-1 receptor antagonist in Behçet’s disease. Rheumatol Int 25, 1–5 (2005). https://doi.org/10.1007/s00296-003-0400-6

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  • DOI: https://doi.org/10.1007/s00296-003-0400-6

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