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 (51C)r 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‐γ, IL‐1β, TNF‐α, 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 ling cancer.