SYNERGISTIC INTERACTIONS BETWEEN IFN-GAMMA AND IFN-BETA IN PRIMING MURINE MACROPHAGES FOR TUMOR-CELL KILLING

The ability of MulFN-.beta. and MulFN-.gamma. to potentiate the development of tumoricidal activity in protease peptone-elicited murine peritoneal macrophages was investigated. Macrophages were stimulated with increasing concentrations of either MulFN-.beta. or MulFN-.gamma., alone and in combination, in the presence of 1 ng/ml lipolysaccharide (LPS). The priming activities attributable to the interferons (IFNs) were quantified using the dose-response curves obtained for these samples. The priming activity observed for mixtures of MulFN-.beta. and MulFN-.gamma. was greater that that expected if MulFN-.beta. and MulFN-.gamma. had acted in an additive manner. Isobologram analysis of data obtained when macrophages were stimulated with combinations of IFNs demonstrated that MulFN-.beta. and MulFN-.gamma. acted synergistically to prime macrophages for tumour cell killing. The greatest degree of syngery was observed when macrophages were stimulated with suboptimal and nearly equivalent concentrations of each class of IFN. Further studies demonstrated that macrophages stimulated with combinations of MulFN-.beta. and MulFn-.gamma. were more sensitive to the trigger signal provided by LPS than were cells primed with either IFN alone. Thus, the synergistic effects observed were quantitative in nature in that macrophages perceived combinations of MulFN-.beta. and MulFN-.gamma. as having priming activities than expected.