PMID- 11848485
OWN - NLM
STAT- MEDLINE
DCOM- 20020312
LR  - 20081121
IS  - 0250-7005 (Print)
IS  - 0250-7005 (Linking)
VI  - 21
IP  - 5
DP  - 2001 Sep-Oct
TI  - Down-regulation of IL-18 receptor in cancer patients: its clinical significance.
PG  - 3285-93
AB  - Interleukin-18 (IL-18) is a powerful inducer of interferon-gamma (IFN-gamma), a 
      key immunoregulatory cytokine. Cellular immune responsiveness, as measured by 
      IL-18-induced IFN-gamma 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-gamma were detected at 2 hours 
      after PBMCs culture and markedly increased thereafter in healthy volunteers. In 
      contrast, IFN-gamma 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-gamma in 
      PBMCs in cancer patients and healthy volunteers by RT-PCR assay. Both mRNA levels 
      of IL-18R and IFN-gamma were significantly decreased in cancer-bearing patients 
      compared with normal controls. These results suggested that IL-18 responsiveness 
      for IFN-gamma 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+ V alpha24+ (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.
FAU - Kobashi, K
AU  - Kobashi K
AD  - First Department of Surgery, Okayama University Medical School, Japan.
FAU - Iwagaki, H
AU  - Iwagaki H
FAU - Yoshino, T
AU  - Yoshino T
FAU - Morimoto, Y
AU  - Morimoto Y
FAU - Kohka, H
AU  - Kohka H
FAU - Kodama, M
AU  - Kodama M
FAU - Nishibori, M
AU  - Nishibori M
FAU - Akagi, T
AU  - Akagi T
FAU - Tanaka, N
AU  - Tanaka N
LA  - eng
PT  - Journal Article
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - 0 (IL18R1 protein, human)
RN  - 0 (Interleukin-18)
RN  - 0 (Interleukin-18 Receptor alpha Subunit)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Interleukin)
RN  - 0 (Receptors, Interleukin-18)
RN  - 187348-17-0 (Interleukin-12)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Down-Regulation
MH  - Female
MH  - Flow Cytometry
MH  - Humans
MH  - Interferon-gamma/biosynthesis/genetics
MH  - Interleukin-12/biosynthesis
MH  - Interleukin-18/pharmacokinetics/pharmacology
MH  - Interleukin-18 Receptor alpha Subunit
MH  - Killer Cells, Natural/cytology/immunology
MH  - Leukocytes, Mononuclear/drug effects/metabolism
MH  - Lymphocyte Subsets
MH  - Male
MH  - Middle Aged
MH  - Neoplasms/genetics/immunology/*metabolism
MH  - RNA, Messenger/biosynthesis/genetics
MH  - Receptors, Interleukin/*biosynthesis/genetics/metabolism
MH  - Receptors, Interleukin-18
MH  - T-Lymphocytes, Cytotoxic/cytology/immunology
EDAT- 2002/02/19 10:00
MHDA- 2002/03/13 10:01
CRDT- 2002/02/19 10:00
PHST- 2002/02/19 10:00 [pubmed]
PHST- 2002/03/13 10:01 [medline]
PHST- 2002/02/19 10:00 [entrez]
PST - ppublish
SO  - Anticancer Res. 2001 Sep-Oct;21(5):3285-93.