Skip to main content

Serum levels of interleukin-1 receptor antagonist (IL-1ra) in thyroid cancer patients

Langenbeck's Archives of Surgery volume 393, pages 275–280 (2008)Cite this article

Abstract

Background and aims

There is growing evidence that cytokines and their antagonists are important in the pathogenesis of various malignancies. While there are several reports on interleukin-1 receptor antagonist (IL-1ra) gene polymorphism and tissue expression, there is only little data available on the impact of IL-1ra serum levels. Therefore, we performed a prospective study, analyzing IL-1ra in thyroid cancer patients.

Materials and methods

We measured preoperative IL-1ra serum levels of 52 consecutive patients with thyroid cancer, 15 with benign adenoma and 27 healthy volunteers. The final histological diagnosis revealed 21 patients with papillary and 8 patients with follicular carcinoma (FTC), while 12 cases of medullary and 11 cases of anaplastic carcinoma (ATC) were observed.

Results

Compared to the control group, serum concentrations of IL-1ra were significantly higher in ATC and FTC patients. Concerning gender differences, this effect reached significance only in women with ATC and FTC. Except for the stage IV disease in ATC, there was no correlation between IL-1ra levels and International Union Against Cancer staging.

Conclusion

The findings of our study indicate that IL-1ra may play an important role in the development of ATC and FTC. Future efforts should focus on the possible application of IL-1ra as a biomarker for the above-mentioned thyroid malignancies.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1

References

  1. Arend WP, Malyak M, Guthridge CJ, Gabay C (1998) Interleukin-1 receptor antagonist: role in biology. Annu Rev Immunol 16:27–55

    PubMed  Article  CAS  Google Scholar 

  2. Dinarello CA (1991) Interleukin-1 and interleukin-1 antagonism. Blood 77:1627–1652

    PubMed  CAS  Google Scholar 

  3. Dinarello CA (1994) The biological properties of interleukin-1. Eur Cytokine Netw 5:517–531

    PubMed  CAS  Google Scholar 

  4. Platanias LC, Vogelzang NJ (1990) Interleukin-1: biology, pathophysiology, and clinical prospects. Am J Med 89:621–629

    PubMed  Article  CAS  Google Scholar 

  5. Arend WP (1990) Interleukin-1 receptor antagonist: discovery, structure and properties. Prog Growth Factor Res 2:193–205

    PubMed  Article  CAS  Google Scholar 

  6. Muzio M, Re F, Sironi M, Polentarutti N, Minty A, Caput D, Ferrara P, Mantovani A, Colotta F (1994) Interleukin-13 induces the production of interleukin-1 receptor antagonist (IL-1ra) and the expression of the mRNA for the intracellular (keratinocyte) form of IL-1ra in human myelomonocytic cells. Blood 83:1738–1743

    PubMed  CAS  Google Scholar 

  7. Janson RW, Hance KR, Arend WP (1991) Production of IL-1 receptor antagonist by human in vitro-derived macrophages. Effects of lipopolysaccharide and granulocyte-macrophage colony-stimulating factor. J Immunol 147:4218–4223

    PubMed  CAS  Google Scholar 

  8. Krzesicki RF, Hatfield CA, Bienkowski MJ, McGuire JC, Winterrowd GE, Chapman DL, Berger AE, McEwan RN, Carter DB, Chosay JG et al (1993) Regulation of expression of IL-1 receptor antagonist protein in human synovial and dermal fibroblasts. J Immunol 150:4008–4018

    PubMed  CAS  Google Scholar 

  9. Dripps DJ, Brandhuber BJ, Thompson RC, Eisenberg SP (1991) Interleukin-1 (IL-1) receptor antagonist binds to the 80-kDa IL-1 receptor but does not initiate IL-1 signal transduction. J Biol Chem 266:10331–10336

    PubMed  CAS  Google Scholar 

  10. Hirsch E, Irikura VM, Paul SM, Hirsh D (1996) Functions of interleukin 1 receptor antagonist in gene knockout and overproducing mice. Proc Natl Acad Sci U S A 93:11008–11013

    PubMed  Article  CAS  Google Scholar 

  11. Gabay C, Smith MF, Eidlen D, Arend WP (1997) Interleukin 1 receptor antagonist (IL-1Ra) is an acute-phase protein. J Clin Invest 99:2930–2940

    PubMed  Article  CAS  Google Scholar 

  12. Prieur AM, Kaufmann MT, Griscelli C, Dayer JM (1987) Specific interleukin-1 inhibitor in serum and urine of children with systemic juvenile chronic arthritis. Lancet 2:1240–1242

    PubMed  Article  CAS  Google Scholar 

  13. Gabay C, Gay-Croisier F, Roux-Lombard P, Meyer O, Maineti C, Guerne PA, Vischer T, Dayer JM (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

    PubMed  Article  CAS  Google Scholar 

  14. Suzuki H, 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

    PubMed  Article  CAS  Google Scholar 

  15. Rogy MA, Coyle SM, Oldenburg HS, Rock CS, Barie PS, Van Zee KJ, Smith CG, Moldawer LL, Lowry SF (1994) Persistently elevated soluble tumor necrosis factor receptor and interleukin-1 receptor antagonist levels in critically ill patients. J Am Coll Surg 178:132–138

    PubMed  CAS  Google Scholar 

  16. Pruitt JH, Welborn MB, Edwards PD, Harward TR, Seeger JW, Martin TD, Smith C, Kenney JA, Wesdorp RI, Meijer S, Cuesta MA, Abouhanze A, Copeland EM 3rd, Giri J, Sims JE, Moldawer LL, Oldenburg HS (1996) Increased soluble interleukin-1 type II receptor concentrations in postoperative patients and in patients with sepsis syndrome. Blood 87:3282–3288

    PubMed  CAS  Google Scholar 

  17. Chensue SW, Warmington KS, Berger AE, Tracey DE (1992) Immunohistochemical demonstration of interleukin-1 receptor antagonist protein and interleukin-1 in human lymphoid tissue and granulomas. Am J Pathol 140:269–275

    PubMed  CAS  Google Scholar 

  18. Lindmark F, Zheng SL, Wiklund F, Balter KA, Sun J, Chang B, Hedelin M, Clark J, Johansson JE, Meyers DA, Adami HO, Isaacs W, Gronberg H, Xu J (2005) Interleukin-1 receptor antagonist haplotype associated with prostate cancer risk. Br J Cancer 93:493–497

    PubMed  Article  CAS  Google Scholar 

  19. Graziano F, Ruzzo A, Santini D, Humar B, Tonini G, Catalano V, Berardi R, Pizzagalli F, Arduini F, Bearzi I, Scartozzi M, Cascinu S, Testa E, Ficarelli R, Magnani M (2005) Prognostic role of interleukin-1beta gene and interleukin-1 receptor antagonist gene polymorphisms in patients with advanced gastric cancer. J Clin Oncol 23:2339–2345

    PubMed  Article  CAS  Google Scholar 

  20. Al-Moundhri MS, Al-Nabhani M, Al-Bahrani B, Burney IA, Al-Madhani A, Ganguly SS, Al-Yahyaee SA, Grant CS (2006) Interleukin-1beta gene (IL-1B) and interleukin 1 receptor antagonist gene (IL-1RN) polymorphisms and gastric cancer risk in an Omani Arab population. Gastric Cancer 9:284–290

    PubMed  Article  CAS  Google Scholar 

  21. Sehouli J, Mustea A, Koensgen D, Chen FC, Lichtenegger W (2003) Interleukin-1 receptor antagonist gene polymorphism is associated with increased risk of epithelial ovarian cancer. Ann Oncol 14:1501–1504

    PubMed  Article  CAS  Google Scholar 

  22. Santtila S, Savinainen K, Hurme M (1998) Presence of the IL-1RA allele 2 (IL1RN*2) is associated with enhanced IL-1beta production in vitro. Scand J Immunol 47:195–198

    PubMed  Article  CAS  Google Scholar 

  23. Danis VA, Millington M, Hyland VJ, Grennan D (1995) Cytokine production by normal human monocytes: inter-subject variation and relationship to an IL-1 receptor antagonist (IL-1Ra) gene polymorphism. Clin Exp Immunol 99:303–310

    PubMed  CAS  Article  Google Scholar 

  24. Gruss HJ, Dolken G, Brach MA, Mertelsmann R, Herrmann F (1992) High concentrations of the interleukin-1 receptor antagonist in serum of patients with Hodgkin's disease. Lancet 340:968

    PubMed  Article  CAS  Google Scholar 

  25. Smith DR, Kunkel SL, Standiford TJ, Chensue SW, Rolfe MW, Orringer MB, Whyte RI, Burdick MD, Danforth JM, Gilbert AR et al (1993) The production of interleukin-1 receptor antagonist by human bronchogenic carcinoma. Am J Pathol 143:794–803

    PubMed  CAS  Google Scholar 

  26. Fujiwaki R, Hata T, Miyazaki K, Kawamura T, Inada K (1997) Elevation of serum interleukin-1 receptor antagonist levels in women with gynaecological cancers. Br J Obstet Gynaecol 104:1407–1408

    PubMed  CAS  Google Scholar 

  27. Oelmann E, Kraemer A, Serve H, Reufi B, Oberberg D, Patt S, Herbst H, Stein H, Thiel E, Berdel WE (1997) Autocrine interleukin-1 receptor antagonist can support malignant growth of glioblastoma by blocking growth-inhibiting autocrine loop of interleukin-1. Int J Cancer 71:1066–1076

    PubMed  Article  CAS  Google Scholar 

  28. Van Le L, Haskill S, Jaffe GJ, Fowler WC Jr (1991) Expression of interleukin-1 and interleukin-1 receptor antagonists in endometrial cancer. Gynecol Oncol 42:161–164

    PubMed  Article  Google Scholar 

  29. Iizuka N, Hazama S, Hirose K, Abe T, Tokuda N, Fukumoto T, Tangoku A, Oka M (1999) Interleukin-1 receptor antagonist mRNA expression and the progression of gastric carcinoma. Cancer Lett 142:179–184

    PubMed  Article  CAS  Google Scholar 

  30. Hefler LA, Ludwig E, Lebrecht A, Zeillinger R, Tong-Cacsire D, Koelbl H, Leodolter S, Tempfer CB (2002) Polymorphisms of the interleukin-1 gene cluster and ovarian cancer. J Soc Gynecol Investig 9:386–390

    PubMed  Article  CAS  Google Scholar 

  31. Lee KM, Park SK, Hamajima N, Tajima K, Choi JY, Noh DY, Ahn SH, Yoo KY, Hirvonen A, Kang D (2006) Genetic polymorphisms of interleukin-1 beta (IL-1B) and IL-1 receptor antagonist (IL-1RN) and breast cancer risk in Korean women. Breast Cancer Res Treat 96:197–202

    PubMed  Article  CAS  Google Scholar 

  32. Wilkinson RJ, Patel P, Llewelyn M, Hirsch CS, Pasvol G, Snounou G, Davidson RN, Toossi Z (1999) Influence of polymorphism in the genes for the interleukin (IL)-1 receptor antagonist and IL-1beta on tuberculosis. J Exp Med 189:1863–174

    PubMed  Article  CAS  Google Scholar 

  33. Speirs V, Kerin MJ, Newton CJ, Walton DS, Green AR, Desai SB, Atkin SL (1999) Evidence for transcriptional activation of ERalpha by IL-1beta in breast cancer cells. Int J Oncol 15:1251–1254

    PubMed  CAS  Google Scholar 

  34. Ito H, Miki C (1999) Profile of circulating levels of interleukin-1 receptor antagonist and interleukin-6 in colorectal cancer patients. Scand J Gastroenterol 34:1139–1143

    PubMed  Article  CAS  Google Scholar 

  35. Fischer E, Van Zee KJ, Marano MA, Rock CS, Kenney JS, Poutsiaka DD, Dinarello CA, Lowry SF, Moldawer LL (1992) Interleukin-1 receptor antagonist circulates in experimental inflammation and in human disease. Blood 79:2196–2200

    PubMed  CAS  Google Scholar 

  36. Von Dossow V, Baur S, Sander M, Tnnesen H, Marks C, Paschen C, Berger G, Spies CD (2007) Propofol increased the interleukin-6 to interleukin-10 ratio more than isoflurane after surgery in long-term alcoholic patients. J Int Med Res 35:395–405

    Google Scholar 

  37. Cai XH, Wang SP, Chen XT, Peng SL, Cao MH, Ye XJ, Yang YZ (2007) Comparison of three analgesic methods for postoperative pain relief and their effects on plasma interleukin-6 concentration following radical surgery for gastric carcinoma. Nan Fang Yi Ke Da Xue Xue Bao 27:387–389

    PubMed  CAS  Google Scholar 

  38. Szczesny TJ, Slotwinski R, Stankiewicz A, Szczygiel B, Zaleska M, Kopacz M (2007) Interleukin 6 and interleukin 1 receptor antagonist as early markers of complications after lung cancer surgery. Eur J Cardiothorac Surg 31:719–724

    PubMed  Article  Google Scholar 

  39. Witkin SS, Gerber S, Ledger WJ (2002) Influence of interleukin-1 receptor antagonist gene polymorphism on disease. Clin Infect Dis 34:204–209

    PubMed  Article  CAS  Google Scholar 

  40. Di Renzo L, Bigioni M, Del Gobbo V, Premrov MG, Barbini U, Di Lorenzo N, De Lorenzo A (2007) Interleukin-1 (IL-1) receptor antagonist gene polymorphism in normal weight obese syndrome: relationship to body composition and IL-1 alpha and beta plasma levels. Pharmacol Res 55:131–138

    PubMed  Article  CAS  Google Scholar 

  41. Ashdown H, Poole S, Boksa P, Luheshi GN (2007) Interleukin-1 receptor antagonist as a modulator of gender differences in the febrile response to lipopolysaccharide in rats. Am J Physiol Regul Integr Comp Physiol 292:R1667–R1674

    PubMed  CAS  Google Scholar 

Download references

Acknowledgement

This paper was supported by the Medical University of Łódź, Grant no. 503-1084-3.

Author information

Affiliations

  1. Department of Endocrine and General Surgery, Medical University of Łódź, Copernicus Memorial Hospital, ul. Pabianicka 62, 93-513, Łódź, Poland

    Sebastian Niedźwiecki, Tomasz Stępień, Krzysztof Kuzdak & Roman Krupiński

  2. Department of Immunoendocrinology, Medical University of Łódź, Łódź, Poland

    Henryk Stępień

  3. Department of General, Visceral and Transplantation Surgery, Charité, University Medicine, Campus Virchow Clinical Centre, Berlin, Germany

    Sebastian Niedźwiecki, Daniel Seehofer, Nada Rayes & Frank Ulrich

Authors
  1. Sebastian Niedźwiecki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tomasz Stępień
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Krzysztof Kuzdak
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Henryk Stępień
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Roman Krupiński
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Daniel Seehofer
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nada Rayes
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Frank Ulrich
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sebastian Niedźwiecki.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Niedźwiecki, S., Stępień, T., Kuzdak, K. et al. Serum levels of interleukin-1 receptor antagonist (IL-1ra) in thyroid cancer patients. Langenbecks Arch Surg 393, 275–280 (2008). https://doi.org/10.1007/s00423-007-0251-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00423-007-0251-9

Keywords

  • Interleukin-1 receptor antagonist
  • Thyroid cancer