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 th e present study, we examined IL-15-mediated induction of killer activi ty of peripheral blood mononuclear cells (MNC) against lung cancer cel l lines, and the regulatory mechanisms of this induction by IL-15. Cyt otoxic activity was measured by Cr-51 release assay. IL-15 at concentr ations of more than 10 ng/ml induced significant killer activity of bl ood 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 induct ion of killer activity against SBC-3 cells. On the other hand, IL-15 h ad no synergistic or additive effect on induction of killer activity b y IL-2. Fresh human monocytes isolated by centrifugal elutriation augm ented the development of killer activity of lymphocytes stimulated by IL-15. As a humoral regulatory factor, IL-4 had a suppressive effect o n induction of killer activity by IL-15. IFN-gamma, IL-1 beta, TNF-alp ha, 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 cancer.