Induction by interferon-alpha of tumoricidal activity of adherent mononuclear cells from human blood: monocytes as responder and effector cells.

Human blood monocytes, separated on a Percoll gradient, were not cytotoxic to allogeneic melanoma (A375) cells. Fluorescent analysis showed that the monocytes were contaminated with up to 2.0% natural killer (NK) cells. The monocytes became tumoricidal on incubation for 24 h with greater than or equal to 1,000 IU/ml interferon-alpha (IFN-alpha) derived from human lymphoblastic leukemia cells. Anti-IFN-alpha antibody abolished the ability of IFN-alpha to render the monocytes tumoricidal, whereas anti-IFN-beta antibody had no effect. Pretreatment of isolated monocyte preparations with anti-NK cell monoclonal antibodies (Leu-7 and Leu-11b), to inhibit NK cell activity, did not affect the cytotoxicity of IFN-alpha-activated monocytes on tumor cells. Full expression of cytotoxicity on tumor cells required the interaction of monocytes with IFN-alpha for 24 h. These results indicate that IFN-alpha directly activates human monocytes to become tumoricidal, although greater than or equal to 1,000 IU/ml IFN-alpha is required for maximal activation.