Down-regulation of IL-18 receptor in cancer patients: Its clinical significance

Kenta Kobashi, Hiromi Iwagaki, Tadashi Yoshino, Yoshinori Morimoto, Hideo Kohka, Masaharu Kodama, Masahiro Nishibori, Tadaatsu Akagi, Noriaki Tanaka

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Interleukin-18 (IL-18) is a powerful inducer of interferon-gamma (IFN-γ), a key immunoregulatory cytokine. Cellular immune responsiveness, as measured by IL-18-induced IFN-γ production from peripheral blood mononuclear cells (PBMCs) in ELISA assay, was evaluated in 10 patients with advanced cancer and in 10 normal controls. Supernatant levels of IFN-γ were detected at 2 hours after PBMCs culture and markedly increased thereafter in healthy volunteers. In contrast, IFN-γ production in cancer patients was not detected during the culture period (0-72 hours). We also measured IL-18-stimulated IL-12 production in healthy volunteers and null response was observed in cancer-bearing patients. Next, we studied mRNA expressions of IL-18 receptor (IL-18R) and IFN-γ in PBMCs in cancer patients and healthy volunteers by RT-PCR assay. Both mRNA levels of IL-18R and IFN-γ were significantly decreased in cancer-bearing patients compared with normal controls. These results suggested that IL-18 responsiveness for IFN-γ production in cancer-bearing patients was impaired. Using flow cytometric analysis, we studied T-cell subsets, CD3- CD56+ (NK cell), CD3+ CD45RO+ (memory T-cell), CD3+ CD95+ (Fas+ T-cell), CD3+ CD4+ (helper T-cell), CD3+ CD8+ (cytotoxic T-cell: CTL) and CD3+ Va24+ (NKT-cell), in cancer patients and normal controls. The NK and cytotoxic T-cells significantly decreased and NKT-cells had decreased tendency in cancer patients compared with normal controls. In contrast, memory T-cells, Fas+T-cells and helper T-cells were all significantly increased in cancer patients compared with normal controls. These results suggested that the underlying mechanism of impaired IL-18 responsiveness in PBMCs from cancer-bearing patients was, at least in part, ascribed to a drastic decrease of NK cells and CTL which constitutively and highly express IL-18R and also attributed to null production of IL-12 which up-regulates IL-18R.

Original languageEnglish
Pages (from-to)3285-3293
Number of pages9
JournalAnticancer Research
Volume21
Issue number5
Publication statusPublished - 2001

Fingerprint

Interleukin-18 Receptors
Down-Regulation
Interferon-gamma
Interleukin-18
Neoplasms
T-Lymphocytes
Blood Cells
Healthy Volunteers
Natural Killer T-Cells
Interleukin-12
Helper-Inducer T-Lymphocytes
Natural Killer Cells
Messenger RNA
T-Lymphocyte Subsets

Keywords

  • Cancer patients
  • IL-18 receptor

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Kobashi, K., Iwagaki, H., Yoshino, T., Morimoto, Y., Kohka, H., Kodama, M., ... Tanaka, N. (2001). Down-regulation of IL-18 receptor in cancer patients: Its clinical significance. Anticancer Research, 21(5), 3285-3293.

Down-regulation of IL-18 receptor in cancer patients : Its clinical significance. / Kobashi, Kenta; Iwagaki, Hiromi; Yoshino, Tadashi; Morimoto, Yoshinori; Kohka, Hideo; Kodama, Masaharu; Nishibori, Masahiro; Akagi, Tadaatsu; Tanaka, Noriaki.

In: Anticancer Research, Vol. 21, No. 5, 2001, p. 3285-3293.

Research output: Contribution to journalArticle

Kobashi, K, Iwagaki, H, Yoshino, T, Morimoto, Y, Kohka, H, Kodama, M, Nishibori, M, Akagi, T & Tanaka, N 2001, 'Down-regulation of IL-18 receptor in cancer patients: Its clinical significance', Anticancer Research, vol. 21, no. 5, pp. 3285-3293.
Kobashi K, Iwagaki H, Yoshino T, Morimoto Y, Kohka H, Kodama M et al. Down-regulation of IL-18 receptor in cancer patients: Its clinical significance. Anticancer Research. 2001;21(5):3285-3293.
Kobashi, Kenta ; Iwagaki, Hiromi ; Yoshino, Tadashi ; Morimoto, Yoshinori ; Kohka, Hideo ; Kodama, Masaharu ; Nishibori, Masahiro ; Akagi, Tadaatsu ; Tanaka, Noriaki. / Down-regulation of IL-18 receptor in cancer patients : Its clinical significance. In: Anticancer Research. 2001 ; Vol. 21, No. 5. pp. 3285-3293.
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