Impaired NK response of cancer patients to IFN-alpha but not to IL-2: correlation with serum immunosuppressive acidic protein (IAP) and role of suppressor macrophage.
In vitro NK responses of cancer patients (N = 21) to rIFN-alpha A and rIL-2 were examined. The serum concentration of IAP (immunosuppressive acidic protein) was determined in parallel. Five out of seven patients whose serum IAP contents were within the normal range (270 micrograms/ml to 470 micrograms/ml), had their NK activities significantly augmented by rIFN-alpha A and rIL-2. On the other hand, NK cells from ten out of fifteen patients whose serum IAP concentrations were 650 micrograms/ml or more, were not activated by rIFN-alpha A. NK cells of these fifteen patients yet were capable of responding to rIL-2. NK cells from cancer patients, however, became responsive to rIFN-alpha A by either removal of adherent cells or treatment with indomethacin. Therefore, macrophages in PBMC of cancer patients with high serum IAP levels seem to selectively suppress NK response to rIFN-alpha A by an indomethacin-sensitive mechanisms. It was further shown that PGE2 was not the mediator of this suppression.
Aso
H
H
Department of Pharmaceutical Sciences, Tohoku University Hospital, Miyagi, Japan.
Tamura
K
K
Yoshie
O
O
Nakamura
T
T
Kikuchi
S
S
Ishida
N
N
D000328:Adult; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D015232:Dinoprostone / Q000096:biosynthesis; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007370:Interferon Type I / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000502:physiology*; D009000:Monocytes / Q000276:immunology; D009363:Neoplasm Proteins / Q000097:blood*; D009369:Neoplasms / Q000097:blood / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D007370:Interferon Type I; D007376:Interleukin-2; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; C030193:immunosuppressive acidic protein; D015232:Dinoprostone; D007213:Indomethacin