Potentiation of the direct anticellular activity of mouse interferons: mutual synergism and interferon concentration dependence

Abstract

Mouse immune (IFN-gamma)2 and virus-type (IFN-alpha/beta) interferons were used separately and in combination in cloning studies with B-16 melanoma cells. IFN-gamma was found to be a more potent mediator of the direct anticellular effect of interferon than was IFN-alpha/beta, as shown not only by a greater sensitivity of B-16 cells to IFN-gamma but also by a steeper slope of the anticellular sensitivity curve of the IFN-gamma. The differences in the slopes of the curves defining their anticellular effect appeared to be inherent in the interferons themselves and not due to an inhibitor of interferon, a stimulator of cell growth, or another factor possessing anticellular activity. The results are consistent with the interpretation that IFN-gamma and IFN-alpha/beta exert their anticellular effects by different mechanisms. The anticellular activity of interferon against B-16 melanoma replication until development was potentiated by mixed preparations of IFN-gamma and IFN-alpha/beta. The potentiation appeared to be an expression of a property of the interferons themselves. Replication units resistant to the potentiated activity of the interferons were not detected. Potentiation levels were dependent on the concentrations of both IFN-gamma and IFN-alpha/beta and continued to increase dramatically as the interferon concentrations increased. Maximum potentiation observed was 214-fold at the highest interferon concentrations used. The data suggested that potentiation is a mutual, synergistic interaction of IFN-gamma and IFN-alpha/beta.