The effectors of killer activity induced by interferon-alpha and gamma in peripheral blood mononuclear cells.
The nature of effectors of interferon (IFN)-alpha or IFN-gamma-induced killer cell activity remains unclear. The aim of this study was to examine killer cell activity induced by IFN-alpha alone, IFN-gamma alone or a combination of both in patients with renal cell carcinoma (RCC) and to determine the phenotypic patterns of these effectors. The study group included 14 patients (12 men and 2 women, median age 64 years, range 36-77) with confirmed RCC. Peripheral blood mononuclear cells (PBMC) from RCC patients or normal volunteers were cultured with IFN-alpha alone, IFN-gamma alone or a combination of both. Cytotoxic activity was assayed against ACHN cells. Subpopulations of effector cells in IFN-induced killer cell activity were characterized by cell sorting. The most effective type of IFN and the optimal concentration of IFN necessary to induce the maximal killer cell activity varied among RCC patients. The killer activity induced by a combination of IFN-alpha and IFN-gamma was significantly greater than that induced by IFN-alpha or IFN-gamma alone. The greatly increased killer activity induced by IFN-alpha and IFN-gamma was seen in the subpopulations CD3(-) CD16(+), CD3(-) CD56(+) and subpopulation CD3(+)CD4(-), CD3(-)CD16(+), CD3(-)CD56(+), CD57(+)CD16(-), respectively. An optimal type of IFN and optimal concentration of IFN seem to increase the effective rate of treatment of RCC. In addition, the role of IFN-alpha seems to be different from that of IFN-gamma in host defense against RCC. A combination treatment with IFN-alpha and IFN-gamma seems to be suitable to increase the effective rate if we could reduce the side effects of IFNs.
Sakaguchi
Miki
M
Department of Urology, Nagasaki University School of Medicine, Japan.
Kubota
Shigehiro
S
Nishikido
Masaharu
M
Taniguchi
Keisuke
K
Inuzuka
Shu
S
Saito
Yutaka
Y
Kanetake
Hiroshi
H
Koga
Shigehiko
S
D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000097:blood; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010641:Phenotype
D016898:Interferon-alpha; D007371:Interferon-gamma