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 language | English |
|---|---|
| Pages (from-to) | 3285-3293 |
| Number of pages | 9 |
| Journal | Anticancer Research |
| Volume | 21 |
| Issue number | 5 |
| Publication status | Published - 2001 |
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Keywords
- Cancer patients
- IL-18 receptor
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Down-regulation of IL-18 receptor in cancer patients
T2 - Its clinical significance
AU - Kobashi, Kenta
AU - Iwagaki, Hiromi
AU - Yoshino, Tadashi
AU - Morimoto, Yoshinori
AU - Kohka, Hideo
AU - Kodama, Masaharu
AU - Nishibori, Masahiro
AU - Akagi, Tadaatsu
AU - Tanaka, Noriaki
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
KW - Cancer patients
KW - IL-18 receptor
UR - http://www.scopus.com/inward/record.url?scp=0035572793&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035572793&partnerID=8YFLogxK
M3 - Article
C2 - 11848485
AN - SCOPUS:0035572793
VL - 21
SP - 3285
EP - 3293
JO - Anticancer Research
JF - Anticancer Research
SN - 0250-7005
IS - 5
ER -