Gastric Cancer

, Volume 12, Issue 2, pp 95–100 | Cite as

Serum interleukin-6 and -10 levels in patients with gastric cancer

  • Masahide Ikeguchi
  • Tomoko Hatada
  • Manabu Yamamoto
  • Takanori Miyake
  • Tomonori Matsunaga
  • Youji Fukumoto
  • Yoshinori Yamada
  • Kenji Fukuda
  • Hiroaki Saito
  • Shigeru Tatebe
Original Article

Abstract

Background

Interleukin-6 (IL-6) is known to be a multifunctional cytokine and IL-10 is an immunosuppressive factor. Both have been reported to be related to the disease prognosis in some human solid tumors. In the present study, we evaluated the clinical significance of preoperative serum IL-6 and IL-10 levels as new tumor markers in patients with gastric cancer (GC).

Methods

Preoperative serum samples from 90 patients with GC and 9 normal healthy volunteers were assayed. Levels of IL-6 and IL-10 were determined by enzyme-linked immunosorbent assay (ELISA). The clinical significance of serum IL-6 and IL-10 levels was evaluated and compared with serum carcinoembryonic antigen (CEA) levels and serum C-reactive protein (CRP) levels in these patients.

Results

The serum level of IL-6 was significantly higher in the GC patients than in the healthy subjects. Serum IL-6 levels were strongly correlated with CRP levels, but did not correlate with CEA or carbohydrate antigen (CA) 19-9 levels. Serum IL-10 levels did not correlate with CEA, CA19-9, or CRP. Strong positive correlations between serum IL-6 levels and tumor size and tumor stage were observed. On the other hand, IL-10 did not correlate with such clinicopathological findings of tumors. However, high serum IL-10 levels were associated with a worse prognosis in the GC patients, independently of their tumor stage.

Conclusion

These findings indicate that serum IL-6 may suggest gastric cancer progression. On the other hand, IL-10 may play an important role in host immunity and the prognosis of GC patients.

Key words

Gastric cancer Interleukin-6 Interleukin-10 Tumor marker 

References

  1. 1.
    Guadagni F, Roselli M, Amato T, Cosimelli M, Mannella E, Perri P, et al. Tumor-associated glycoprotein-72 serum levels complement carcinoembryonic antigen levels in monitoring patients with gastrointestinal carcinoma. A longitudinal study. Cancer 1991;68:2443–2450.PubMedCrossRefGoogle Scholar
  2. 2.
    Ikeguchi M, Katano K, Saitou H, Tsujitani S, Maeta M, Kaibara N. Pre-operative serum levels of CA72-4 in patients with gastric adenocarcinoma. Hepatogastroenterology 1997;44:866–871.PubMedGoogle Scholar
  3. 3.
    Hirano T, Akira S, Taga T. Biological and clinical aspects of interleukin-6. Immunol Today 1990;11:443–449.PubMedCrossRefGoogle Scholar
  4. 4.
    Leu CM, Wong FH, Chang C, Huang SF, Hu CP. Interleukin-6 acts as an antiapoptotic factor in human esophageal carcinoma cells through the activation of both STAT3 and mitogen-activated protein kinase pathways. Oncogene 2003;22:7809–7818.PubMedCrossRefGoogle Scholar
  5. 5.
    Watson JM, Sensintaffar JL, Berek JS, Martinez-Maza O. Constitutive production of IL-6 by ovarian cancer cell lines and by primary ovarian tumor cultures. Cancer Res 1990;50:6959–6965.PubMedGoogle Scholar
  6. 6.
    Bataille R, Jourdan M, Zhang XG, Klein B. Serum levels of interleukin 6, a potent myeloma growth factor, as a reflection of disease severity in plasma cell dyscrasias. J Clin Invest 1989;84:2008–2011.PubMedCrossRefGoogle Scholar
  7. 7.
    Tsukamoto T, Kumamoto Y, Miyao N, Masumori N, Takahashi A, Yanase M. Interleukin-6 in renal cell carcinoma. J Urol 1992;148:1778–1782.PubMedGoogle Scholar
  8. 8.
    Seguchi T, Yokokawa K, Sugao H, Nakano E, Sonoda T, Okuyama A. Interleukin-6 activity in urine and serum in patients with bladder carcinoma. J Urol 1992;148:791–794.PubMedGoogle Scholar
  9. 9.
    Gallo O, Gori AM, Attanasio M, Martini F, Paola G, Storchi OF, et al. Acute-phase proteins and interleukin-6 serum level in head and neck cancer. Arch Otolaryngol 1992;118:1336–1337.Google Scholar
  10. 10.
    Berek JS, Chung C, Kaldi K, Watson JM, Knox RM, Martínez-Maza O. Serum interleukin-6 levels correlate with disease status in patients with epithelial ovarian cancer. Am J Obstet Gynecol 1991;164:1038–1043.PubMedGoogle Scholar
  11. 11.
    Goydos JS, Brumfield AM, Frezza E, Booth A, Lotze MT, Carty SE. Marked elevation of serum interleukin-6 in patients with cholangiocarcinoma. Validation of utility as a clinical marker. Ann Surg 1998;227:398–404.PubMedCrossRefGoogle Scholar
  12. 12.
    Howard M, O’Garra A, Ishida H, de Waal Malefyt R, de Vries J. Biologic properties of interleukin-10. J Clin Immunol 1992;12:239–247.PubMedCrossRefGoogle Scholar
  13. 13.
    Holland G, Zlotnik A. Interleukin-10 and cancer. Cancer Invest 1993;11:751–758.PubMedCrossRefGoogle Scholar
  14. 14.
    Nabioullin R, Sone S, Mizuno K, Yano S, Nishioka Y, Haku T, et al. Interleukin-10 is a potent inhibitor of tumor cytotoxicity by human monocytes and alveolar macrophages. J Leukocyte Biol 1994;55:437–442.PubMedGoogle Scholar
  15. 15.
    Fortis C, Foppoli M, Gianotti L, Galli L, Citterio G, Consogno G, et al. Increased interleukin-10 serum levels in patients with solid tumors. Cancer Lett 1996;104:1–5.PubMedCrossRefGoogle Scholar
  16. 16.
    Merville P, Rousset F, Banchereau J, Klein B, Betaille R. Serum interleukin-10 in early stage multiple myeloma. Lancet 1992;340:1544–1545.PubMedCrossRefGoogle Scholar
  17. 17.
    Blay JY, Burdin N, Rousset F, Lenoir G, Biron P, Philip T, et al. Serum interleukin-10 in non-Hodgkin’s lymphoma: a prognostic factor. Blood 1993;82:2169–2174.PubMedGoogle Scholar
  18. 18.
    Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma — 2nd English edition. Gastric Cancer 1998;1:10–24.PubMedCrossRefGoogle Scholar
  19. 19.
    Choi SR, Jang JS, Lee JH, Roh MH, Kim MC, Lee WS, et al. Role of serum tumor markers in monitoring for recurrence of gastric cancer following radical gastrectomy. Dig Dis Sci 2006;51:2081–2086.PubMedCrossRefGoogle Scholar
  20. 20.
    Yamashita H, Kitayama J, Nagawa H. Hyperfibrinogenemia is a useful predictor for lymphatic metastasis in human gastric cancer. Jpn J Clin Oncol 2005;35:595–600.PubMedCrossRefGoogle Scholar
  21. 21.
    Ikuta S, Miki C, Tanaka K, Konishi N, Mohri Y, Tonouchi H, et al. Serum immunosuppressive acidic protein as an interleukin-6 related index of deteriorating condition in gastric cancer patients. Dig Surg 2003;20:532–538.PubMedCrossRefGoogle Scholar
  22. 22.
    Ashizawa T, Okada R, Suzuki Y, Takagi M, Yamazaki T, Sumi T, et al. Clinical significance of interleukin-6 (IL-6) in the spread of gastric cancer: role of IL-6 as a prognostic factor. Gastric Cancer 2005;8:124–131.PubMedCrossRefGoogle Scholar
  23. 23.
    Castell JV, Gomes-Lechon MJ, David M, Fabra R, Trullenque R, Heinrich PC. Acute-phase response of human hepatocytes: regulation of acute-phase protein synthesis by interleukin-6. Hepatology 1990;12:1179–1186.PubMedCrossRefGoogle Scholar
  24. 24.
    Ito R, Yasui W, Kuniyasu H, Yokozaki H, Tahara E. Expression of interleukin-6 and its effect on the cell growth of gastric carcinoma cell lines. Jpn J Cancer Res 1997;88:953–958.PubMedGoogle Scholar
  25. 25.
    Moore KW, O’Garra A, de Waal Malefyt R, Vieira P, Mosmann TR. Interleukin 10. Annu Rev Immunol 1993;11:165–190.PubMedCrossRefGoogle Scholar
  26. 26.
    Chau GY, Wu CW, Lui WY, Chang TJ, Kao HL, Wu LH, et al. Serum interleukin-10 but not interleukin-6 is related to clinical outcome in patients with resectable hepatocellular carcinoma. Ann Surg 2000;231:552–558.PubMedCrossRefGoogle Scholar
  27. 27.
    Matsuguchi I, Okamura S, Kawasaki C, Niho Y. Production of interleukin-6 from human liver cell lines: production of interleukin-6 is not concurrent with the production of α-fetoprotein. Cancer Res 1990;50:7457–7459.PubMedGoogle Scholar
  28. 28.
    Sakamoto T, Saito H, Tatebe S, Tsujitani S, Ozaki M, Ito H, et al. Interleukin-10 expression significantly correlates with minor CD8+ T-cell infiltration and high microvessel density in patients with gastric cancer. Int J Cancer 2006;118:1909–1914.PubMedCrossRefGoogle Scholar

Copyright information

© The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2009

Authors and Affiliations

  • Masahide Ikeguchi
    • 1
  • Tomoko Hatada
    • 1
  • Manabu Yamamoto
    • 1
  • Takanori Miyake
    • 1
  • Tomonori Matsunaga
    • 1
  • Youji Fukumoto
    • 1
  • Yoshinori Yamada
    • 1
  • Kenji Fukuda
    • 1
  • Hiroaki Saito
    • 1
  • Shigeru Tatebe
    • 1
  1. 1.Department of Surgery, Division of Surgical Oncology, Faculty of MedicineTottori UniversityYonagoJapan

Personalised recommendations