[Induction of human monocyte-mediated tumor cell killing by alpha or beta interferon]

Human blood monocytes, separated on a continuous percoll gradient, were not cytotoxic to allogeneic A375 melanoma cells. The monocyte monolayers were activated to become tumoricidal by incubation for 24 hr with interferon (IFN)-alpha or beta at concentrations of more than 1,000 IU/ml. Significant and reproducible activation of the monocytes was achieved by incubating them with 10,000 IU/ml of IFN-alpha or IFN-beta for 24 hr. Similarly, suspended, but not plated, monocytes were activated to a tumoricidal state by interaction with IFN-alpha or IFN-beta. Monocytes that had lost tumoricidal activity during culture, were reactivated by a second exposure to IFN-alpha. Fluorescence analysis showed that the monocyte-rich adherent monolayers were contaminated with up 2.0% of natural killer (NK) cells. Pretreatment of isolated monocyte preparations with anti-NK cell monoclonal antibody (Leu-11b) to deplete them of NK cell activity did not inhibit the monocyte-mediated cytotoxicity. These results indicate that human monocytes are rendered tumoricidal by direct interaction with IFN-alpha or IFN-beta, although more than 1,000 IU/ml of IFN-alpha or IFN-beta is required for maximal expression of monocyte activation.