Skip to main content

Advertisement

SpringerLink
Log in

Continuity of cytokine activation in patients with familial Mediterranean fever

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

Abstract

Familial Mediterranean fever (FMF) is a recessively inherited inflammatory disorder, characterized by recurrent attacks of fever and polyserositis. It has been considered that miscellaneous cytokines take part in the pathogenesis of the disease. The aim of this study was to investigate serum levels of soluble interleukin-2 receptor (sIL-2R), interleukin-6 (IL-6), and interleukin-10 (IL-10) in patients with FMF. The study included 42 patients with FMF (3 females, 39 males, mean age: 24.43 years) and 20 healthy volunteers as the control group (18 males, 2 females, mean age: 23.2 years). The patients were chosen according to Eliakim criteria. After recording their history and performing an examination, leukocyte counts, erythrocyte sedimentation rates (ESR), C-reactive protein (CRP), fibrinogen, sIL-2R, IL-6, and IL-10 levels were measured before and during attacks. A significant increase was found in leukocyte (p<0.001), ESR (p<0.001), CRP (p<0.001), and fibrinogen (p<0.001) levels of the patient group in the attack period compared to those in the quiescent state. sIL-2R (p=0.019) and IL-6 (p<0.001) levels showed significant increases during attacks compared to the levels before an attack. There was no significant difference between IL-10 levels. The levels of the three cytokines were significantly high both before and during the attacks compared to the control group. As a result, the elevation of sIL-2R and IL-6 levels both before and during the attacks compared to control group suggests the existence of continuous cytokine activation in the patients. No significant increase in the IL-10 levels in spite of the significant rise of sIL-2R and IL-6 during attacks supports the notion of inflammation and also reveals that compensation by anti-inflammatory IL-10 does not seem to occur.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Sohar E, Gafni J, Pras M, Heller H (1967) Familial Mediterranean fever: a survey of 470 cases and review of the literature. Am J Med 43:227–253

    CAS  PubMed  Google Scholar 

  2. Schattner A, Lachmi M, Livneh A, Pras M, Hahn T (1991) Tumor necrosis factor in familial Mediterranean fever. Am J Med 90:434–438

    CAS  PubMed  Google Scholar 

  3. Erken E, Günesacar R, Ozbek S, Konca K (1996) Serum soluble interleukin-2 receptor levels in familial Mediterranean fever. Ann Rheum Dis 55:852–855

    CAS  PubMed  Google Scholar 

  4. Ozyılkan E, Simsek H, Telatar H (1992) Tumor necrosis factor in familial Mediterranean fever. Am J Med 92:579–580

    CAS  PubMed  Google Scholar 

  5. Rozenbaum M, Katz R, Rozner I, Pollack S (1992) Decreased interleukin 1 activity released from circulating monocytes of patients with familial Mediterranean fever during in vitro stimulation by lipopolysaccharide. J Rheumatol 19:416–418

    CAS  PubMed  Google Scholar 

  6. Notarnicola C, Didelot MN, Seguret F, Demaille J, Touitou I (2002) Enhanced cytokine mRNA levels in attack-free patients with familial Mediterranean fever. Genes Immun 3:43–45

    Article  CAS  PubMed  Google Scholar 

  7. Mege JL, Dilşen 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 

  8. Kishimoto T (1989) The biology of interleukin-6. Blood 74:1-10

    CAS  PubMed  Google Scholar 

  9. Moore KW, O’Garra A, de Waal Malefyt R, Vieira P, Mosmann TR (1993) Interleukin-10. Annu Rev Immunol 11:165–190

    CAS  PubMed  Google Scholar 

  10. Eliakim M, Levy M, Ehrenfeld M (1981) Recurrent polyserositis (familial Mediterranean fever, periodic disease). Elsevier/North-Holland Biomedical Press, Amsterdam

  11. International Committee for Standardization in Haematology (1988) Guidelines on selection of laboratory tests for monitoring the acute phase response. J Clin Pathol 41:1203–1212

    PubMed  Google Scholar 

  12. Whicher JT, Bell AM, Southall PJ (1981) Measurements in clinical management. Diagn Med 4:62–80

    Google Scholar 

  13. Ilfeld D, Weil S, Kuperman O (1981) Immunoregulatory abnormalities in familial Mediterranean fever. Clin Immunol Immunopathol 18:261–267

    Article  CAS  PubMed  Google Scholar 

  14. Melamed A, Cabili S, Zakuth V, Spirer Z (1988) The immune regulation in familial Mediterranean fever (FMF). J Clin Lab Immunol 26:125–128

    CAS  PubMed  Google Scholar 

  15. Campen DH, Horwitz DA, Quismorio FP Jr, Ehresmann GR, Martin WJ (1988) Serum levels of interleukin-2 receptor and activity of rheumatic diseases characterized by immune system activation. Arthritis Rheum 31:1358–1364

    CAS  PubMed  Google Scholar 

  16. Wolf RE, Brelsford WG (1988) Soluble interleukin-2 receptors in systemic lupus erythematosus. Arthritis Rheum 31:729–735

    CAS  PubMed  Google Scholar 

  17. Keystone EC, Snow KM, Bombardier C, Chang CH, Nelson DL, Rubin LA (1988) Elevated soluble interleukin-2 receptor levels in the sera and synovial fluids of patients with rheumatoid arthritis. Arthritis Rheum 31:844–849

    CAS  PubMed  Google Scholar 

  18. Rubin LA (1990) The soluble interleukin-2 receptor in rheumatic disease. Arthritis Rheum 33:1145–1148

    CAS  PubMed  Google Scholar 

  19. Oppenheim JJ, Ruscetti FW, Faltynek C (1994) Cytokines. In: Stites P, Terr AI, Parslow TG (eds) Basic and clinical immunology, 8th edn. Appleton and Lange, Northwalk, pp 105–123

  20. Tilg H, Trehu E, Atkins MB, Dinarello CA, Mier JW (1994) Interleukin-6 (IL-6) as an anti-inflammatory cytokine: induction of circulating IL-1 receptor antagonist and soluble tumor necrosis factor receptor p55. Blood 83:113–118

    CAS  PubMed  Google Scholar 

  21. Drenth JPH, van Deuren M, van der Ven-Jongekrijg J, Schalkwijk CG, van der Meer JWM (1995) Cytokine activation during attacks of the hyperimmunoglobulinemia D and periodic fever syndrome. Blood 85:3586–3593

    CAS  PubMed  Google Scholar 

  22. Gang N, Drenth JPH, Langevitz P, Zemer D, Brezniak N, Pras M, van der Meer JWM, Livneh A (1999) Activation of the cytokine network in familial Mediterranean fever. J Rheum 26:890–897

    CAS  PubMed  Google Scholar 

  23. Kiraz S, Ertenli I, Arici M, Calguneri M, Haznedaroglu I, Celik I, Pay S, Kirazli S (1988) Effects of colchicine on inflammatory cytokines and selectins in familial Mediterranean fever. Clin Exp Rheumatol 16:721–724

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gastroenterology, Gulhane School of Medicine, 06018, Etlik-Ankara, Turkey

    Sait Bagci, Bulent Toy, Ahmet Tuzun, Yuksel Ates, Murat Aslan, Mustafa Gulsen, Necmettin Karaeren & Kemal Dagalp

  2. Department of Immunology, Gulhane School of Medicine, Ankara, Turkey

    Ali Inal

Authors
  1. Sait Bagci
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bulent Toy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ahmet Tuzun
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuksel Ates
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Murat Aslan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ali Inal
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mustafa Gulsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Necmettin Karaeren
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kemal Dagalp
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sait Bagci.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bagci, S., Toy, B., Tuzun, A. et al. Continuity of cytokine activation in patients with familial Mediterranean fever. Clin Rheumatol 23, 333–337 (2004). https://doi.org/10.1007/s10067-004-0925-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-004-0925-4

Keywords

Search

Navigation