Recombinant interferons or interleukin-2 increase cytotoxicity by human monocytes and NK cells

Human peripheral blood monocytes and NK cell enriched lymphocytes were purified by counterflow centrifugal elutriation. The cell populations were characterized by surface marker analysis using monoclonal antibodies. A variety of molecules were found to be capable of activating monocytes and NK cells to enhanced tumoricidal activity. Tumoricidal activity was evaluated using a colorimetric microassay. Numbers of tumor cell targets surviving exposure to monocytes or NK cells were calculated by computer analysis of colorimetric data derived by target cell-dependent dye reduction. The results indicated that monocyte effector cells were cytotoxic to the NK sensitive K562 cell line and to the monocyte sensitive TU5 line. Depletion of NK contaminants from the monocyte population by complement mediated cytolysis did not affect the capacity of the monocytes to kill either target. Monocyte mediated cytotoxicity was enhanced by treatment of the monocytes with recombinant IFN-alpha, IFN-beta, or IFN-tau; each in a dose-dependent manner. Simultaneous treatment of monocytes with IFN-alpha and IFN-tau resulted in additive but not synergistic effects. NK cell cytotoxicity was enhanced by treatment with IL-2 or IFN-tau. Enhancement of monocyte and NK cell cytotoxicity by IFN or IL-2 was dependent upon the time in culture of the effector cells, the duration of the effector phase, and the effector to target cell ratio. IFN or IL-2 treatment alone did not reduce target cell viability. The results suggest that monocytes as well as NK cells are capable of providing a natural defence against neoplasia, that monocytes can kill NK targets and NK cells can kill monocyte targets, and that these cytotoxic activities are enhanced by IFN or IL-2.