Cancer Immunology, Immunotherapy

, Volume 55, Issue 4, pp 394–403

Interferon-α/β upregulate IL-15 expression in vitro and in vivo: analysis in human hepatocellular carcinoma cell lines and in chronic hepatitis C patients during interferon-α/β treatment

Authors

    • Department of General MedicineKyushu University Hospital
  • Shigeki Nabeshima
    • Department of General MedicineKyushu University Hospital
  • Masayuki Murata
    • Department of General MedicineKyushu University Hospital
  • Yong Chong
    • Department of General MedicineKyushu University Hospital
  • Norihiro Furusyo
    • Department of General MedicineKyushu University Hospital
  • Hideyuki Ikematsu
    • Department of General MedicineKyushu University Hospital
  • Jun Hayashi
    • Department of General MedicineKyushu University Hospital
Original Article

DOI: 10.1007/s00262-005-0005-x

Cite this article as:
Yamaji, K., Nabeshima, S., Murata, M. et al. Cancer Immunol Immunother (2006) 55: 394. doi:10.1007/s00262-005-0005-x

Abstract

Type I interferon (IFN) possesses antiviral and antitumor activities and also having an immune regulatory effect, activating cellular immune response and upregulating several cytokines. Recent study has shown that type I IFN upregurates the dendritic cell production of IL-15 capable of activating natural killer cells and CD8+ memory T lymphocytes. However, it is still unknown if type I IFN induces IL-15 production in non-immune cells and if type I IFN affects IL-15 production in vivo. The present study investigated the effect of type I IFNs on IL-15 expression in hepatocellular carcinoma (HCC) cell lines in vitro and in patients with chronic hepatitis C in vivo. When three HCC cell lines, Huh7, HepG2, and JHH4 were cultured in vitro, IFN upregulation of IL-15 expression was observed at both the mRNA and protein levels. In experiments using Huh7 cells, upregulation of IL-15 expression occurred within 24 h of the start of IFN stimulation, and both IFN-α and -β dose-dependently increased IL-15 production in the range from 100 U/ml to 10,000 U/ml of concentration. IFN-β showed stronger activity in IL-15 production induction in vitro than IFN-α. For in vivo examination, sera were obtained from 21 chronic hepatitis C patients treated with IFN and 29 healthy individuals, and the serum IL-15 level was quantified by ELISA. The serum IL-15 level of chronic hepatitis C patients before IFN treatment was similar to that of the healthy controls and significantly increased only during the IFN administration period. These results confirm that IFN-α/β induce IL-15 production and also suggest that IL-15 may be associated with type I IFN-induced immune response.

Copyright information

© Springer-Verlag 2005