Induction by interleukin-15 of human killer cell activity against lung cancer cell lines and its regulatory mechanisms.
Interleukin (IL)-15 is a novel cytokine with IL-2-like activity. In the present study, we examined IL-15-mediated induction of killer activity of peripheral blood mononuclear cells (MNC) against lung cancer cell lines, and the regulatory mechanisms of this induction by IL-15. Cytotoxic activity was measured by 51Cr release assay. IL-15 at concentrations of more than 10 ng/ml induced significant killer activity of blood MNC against a small cell lung cancer cell line (SBC-3), as well as Daudi cells, and 50 ng/ml was considered its optimal concentration. A time course study revealed that an incubation period of 4-6 days was optimal for induction of killer activity. MNC cultured with IL-15 also exhibited killer activity against other lung cancer cell lines (H-69, N-291 and PC-9 cells). IL-15 and IL-12 had additive effects on induction of killer activity against SBC-3 cells. On the other hand, IL-15 had no synergistic or additive effect on induction of killer activity by IL-2. Fresh human monocytes isolated by centrifugal elutriation augmented the development of killer activity of lymphocytes stimulated by IL-15. As a humoral regulatory factor, IL-4 had a suppressive effect on induction of killer activity by IL-15. IFN-gamma, IL-1beta, TNF-alpha, IL-6 or IL-10 had no effect on induction of killer activity by IL-15 at the optimal concentration. These results suggest that IL-15 has potential for the immunotherapy of lung cancers.
Takeuchi
E
E
Third Department of Internal Medicine, University of Tokushima School of Medicine, Kuramoto-cho.
Yanagawa
H
H
Yano
S
S
Haku
T
T
Sone
S
S
D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004357:Drug Synergism; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology; D019409:Interleukin-15 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured
D016207:Cytokines; D019409:Interleukin-15; D018664:Interleukin-12; D015847:Interleukin-4