Potentiation of the Antiviral and Anticellular Activities of Interferons by Mixtures of HuIFN-γ and HuIFN-α or HuIFN-β

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Abstract
Treatment of transformed human amnion WISH cells or human diploid fibroblasts (FS-4) or human fibroblasts trisomic for chromosome 21 (GM2767) with mixtures of human interferon gamma (HuIFN-gamma) and either natural leukocyte HuIFN-alpha or recombinant HuIFN alpha 2 or natural fibroblast HuIFN-beta resulted in potentiation of the antiviral activity of these IFNs. Pretreatment for 22 h of WISH cells with HuIFN-gamma followed by the addition of either HuIFN-alpha or HuIFN-beta resulted in significant potentiation of the antiviral action of these IFNs. The range of potentiation was 3 to 15-fold. Similar potentiation was observed when these IFNs were added simultaneously to the cells. Pretreatment for 22 h of WISH cells with either HuIFN-alpha or HuIFN-beta followed by the addition of HuIFN-gamma also resulted in significant increase of the antiviral protection against virus yield (3 to 39-fold). The level of the potentiation was higher in comparison with the antiviral activity observed when all these IFNs were added at the same time. Treatment of human FS-4 and GM2767 fibroblasts with HuIFN-gamma and either HuIFN-alpha or HuIFN-beta revealed potentiation of anticellular properties of these IFNs. The level of potentiation of anticellular activity was in the range of 2.7- to 9.4-fold. In the majority of the experiments, maximum potentiation of either antiviral or anti-cellular activity was observed when mixtures of equivalent concentrations of IFNs were used. The antiviral and anticellular functions of natural or recombinant IFN-alpha and fibroblast IFN-beta were potentiated usually to a similar degree by the presence of IFN-gamma. In contrast, combinations of HuIFN-alpha (natural or recombinant) and HuIFN-beta, in the absence of HuIFN-gamma, did not potentiate the anticellular or antiviral activity.