STIMULATION OF CYTOLYTIC ACTIVITY BY INTERLEUKIN-10

Interleukin-10 (IL-10), originally identified as an inhibitor of cytokine and monokine synthesis [e.g., IL-2, interferon-gamma (IFN-gamma), and tumor necrosis factor (TNF-alpha)], modulates a wide range of immunologic activities. In the present study we have examined the induction of non-major histocompatibility complex-restricted cytolytic activity in human peripheral blood mononuclear cells (PBMCs). PBMCs incubated with human IL-10 for 3 days were used as effector cells in cytotoxicity (i.e., Cr-51 release) assays against a panel of human tumor cells. In a concentration-dependent manner, IL-10 stimulated or potentiated lytic activity against several human tumor cell lines. Induction of cytolytic activities by IL-10 was neutralized by anti-IL-10 monoclonal antibodies but not by antibodies against IFN-gamma or TNF-alpha. Co-incubation of PBMCs with IL-10 and IL-2 or IL-10 and IFN-alpha augmented cytolytic activity, in particular at lower effector-to-target ratios. IL-2-induced release of TNF-alpha was dramatically reduced by IL-10; however, the expression of lymphokine-activated killer (LAK) activity was not affected. PBMCs preactivated with IL-10 before addition of IL-2 displayed higher levels of LAK activity. Inhibition of IL-2-driven LAK activity by IL-4 is alleviated by IL-10. Finally, IL-10 is not affected by inhibitors of IL-2, such as IL,4 and transforming growth factor-beta. Potential application of IL-10 to anti-tumor therapies is discussed.