POTENTIATION OF THE DIRECT ANTI-CELLULAR ACTIVITY OF MOUSE INTERFERONS - MUTUAL SYNERGISM AND INTERFERON CONCENTRATION-DEPENDENCE

  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (3) , 869-875
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 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 possesing 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 unit 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. Potentiation may be a mutual, synergistic interaction of IFN-.gamma. and IFN-.alpha./.beta.