Langenbeck's Archives of Surgery

, Volume 393, Issue 3, pp 275–280

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

  • Sebastian Niedźwiecki
  • Tomasz Stępień
  • Krzysztof Kuzdak
  • Henryk Stępień
  • Roman Krupiński
  • Daniel Seehofer
  • Nada Rayes
  • Frank Ulrich
Original 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.

Keywords

Interleukin-1 receptor antagonist Thyroid cancer 

References

  1. 1.
    Arend WP, Malyak M, Guthridge CJ, Gabay C (1998) Interleukin-1 receptor antagonist: role in biology. Annu Rev Immunol 16:27–55PubMedCrossRefGoogle Scholar
  2. 2.
    Dinarello CA (1991) Interleukin-1 and interleukin-1 antagonism. Blood 77:1627–1652PubMedGoogle Scholar
  3. 3.
    Dinarello CA (1994) The biological properties of interleukin-1. Eur Cytokine Netw 5:517–531PubMedGoogle Scholar
  4. 4.
    Platanias LC, Vogelzang NJ (1990) Interleukin-1: biology, pathophysiology, and clinical prospects. Am J Med 89:621–629PubMedCrossRefGoogle Scholar
  5. 5.
    Arend WP (1990) Interleukin-1 receptor antagonist: discovery, structure and properties. Prog Growth Factor Res 2:193–205PubMedCrossRefGoogle Scholar
  6. 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 83:1738–1743PubMedGoogle Scholar
  7. 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 147:4218–4223PubMedGoogle Scholar
  8. 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 150:4008–4018PubMedGoogle Scholar
  9. 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 266:10331–10336PubMedGoogle Scholar
  10. 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 93:11008–11013PubMedCrossRefGoogle Scholar
  11. 11.
    Gabay C, Smith MF, Eidlen D, Arend WP (1997) Interleukin 1 receptor antagonist (IL-1Ra) is an acute-phase protein. J Clin Invest 99:2930–2940PubMedCrossRefGoogle Scholar
  12. 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 2:1240–1242PubMedCrossRefGoogle Scholar
  13. 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 37:1744–1751PubMedCrossRefGoogle Scholar
  14. 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 38:1055–1059PubMedCrossRefGoogle Scholar
  15. 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 178:132–138PubMedGoogle Scholar
  16. 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 87:3282–3288PubMedGoogle Scholar
  17. 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 140:269–275PubMedGoogle Scholar
  18. 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 93:493–497PubMedCrossRefGoogle Scholar
  19. 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 23:2339–2345PubMedCrossRefGoogle Scholar
  20. 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 9:284–290PubMedCrossRefGoogle Scholar
  21. 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 14:1501–1504PubMedCrossRefGoogle Scholar
  22. 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 47:195–198PubMedCrossRefGoogle Scholar
  23. 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 99:303–310PubMedCrossRefGoogle Scholar
  24. 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 340:968PubMedCrossRefGoogle Scholar
  25. 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 143:794–803PubMedGoogle Scholar
  26. 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 104:1407–1408PubMedGoogle Scholar
  27. 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 71:1066–1076PubMedCrossRefGoogle Scholar
  28. 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 42:161–164PubMedCrossRefGoogle Scholar
  29. 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 142:179–184PubMedCrossRefGoogle Scholar
  30. 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 9:386–390PubMedCrossRefGoogle Scholar
  31. 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 96:197–202PubMedCrossRefGoogle Scholar
  32. 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 189:1863–174PubMedCrossRefGoogle Scholar
  33. 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 15:1251–1254PubMedGoogle Scholar
  34. 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 34:1139–1143PubMedCrossRefGoogle Scholar
  35. 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 79:2196–2200PubMedGoogle Scholar
  36. 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 35:395–405Google Scholar
  37. 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 27:387–389PubMedGoogle Scholar
  38. 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 31:719–724PubMedCrossRefGoogle Scholar
  39. 39.
    Witkin SS, Gerber S, Ledger WJ (2002) Influence of interleukin-1 receptor antagonist gene polymorphism on disease. Clin Infect Dis 34:204–209PubMedCrossRefGoogle Scholar
  40. 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 55:131–138PubMedCrossRefGoogle Scholar
  41. 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–R1674PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Sebastian Niedźwiecki
    • 1
    • 3
  • Tomasz Stępień
    • 1
  • Krzysztof Kuzdak
    • 1
  • Henryk Stępień
    • 2
  • Roman Krupiński
    • 1
  • Daniel Seehofer
    • 3
  • Nada Rayes
    • 3
  • Frank Ulrich
    • 3
  1. 1.Department of Endocrine and General SurgeryMedical University of Łódź, Copernicus Memorial HospitalŁódźPoland
  2. 2.Department of ImmunoendocrinologyMedical University of ŁódźŁódźPoland
  3. 3.Department of General, Visceral and Transplantation Surgery, Charité, University MedicineCampus Virchow Clinical CentreBerlinGermany

Personalised recommendations