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

Treatment of transformed human amnion WISH cells or human diploid fibroblasts (FS-4) or human fibroblasts trisomie for chromosome 21 (GM₂₇₆₇) with mixtures of human interferon γ (HuIFN-γ) and either natural leukocyte HuIFN-α or recombinant HuIFNα₂ or natural fibroblast HuIFN-β resulted in potentiation of the antiviral activity of these IFNs.

Pretreatment for 22 h of WISH cells with HuIFN-γ followed by the addition of either HuIFN-α or HuIFN-β 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-α or HuIFN-β followed by the addition of HuIFN-γ 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-γ and either HuIFN-α or HuIFN-β 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 anticellular activity was observed when mixtures of equivalent concentrations of IFNs were used. The antiviral and anticellular functions of natural or recombinant IFN-α and fibroblast IFN-β were potentiated usually to a similar degree by the presence of IFN-γ. In contrast, combinations of HuIFN-α (natural or recombinant) and HuIFN-β, in the absence of HuIFN-γ, did not potentiate the anticellular or antiviral activity.