Synergistic anticellular and antiviral activities of human recombinant interferon-.GAMMA. and -.BETA..

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Abstract
The synergism of anticellular and antiviral activities of recombinant human interferon-γ (ReIFN-γ) and recombinant human interferon-β (ReIFN-β) was examined in vitro using human melanoma SK-MEL-28 cells. Some differences were detected in the kinetics of anticellular activity between both IFNs, namely the inhibitory effect of ReIFN-β occurred earlier than that of ReIFN-γ. Significant synergism was detected in the anticellular activity of both IFNs when growth curves and isobolograms were examined. A difference between ReIFN-γ and ReIFN-β was also detected in activiral activity. The antiviral activity of ReIFN-γ against vesicular stomatitis virus (VSV) was significantly weaker than that of ReIFN-β, even though both IFNs exhibited almost equivalent antiviral activities against Sindbis virus. However, ReIFN-γ and ReIFN-β exhibited synergistic antiviral activities against both VSV and Sindbis virus. The analysis of cell cycle distribution by flow cytometry revealed that there were some differences in the distribution pattern between cells treated with ReIFN-γ alone, ReIFN-β alone, or ReIFN-γ and ReIFN-β in combination. ReIFN-β induced a prolongation or accumulation of S phase, whereas the effect of ReIFN-γ was cycle-nonspecific. The combination of ReIFN-γ and ReIFN-β induced a decrease of G1 phase and an increase of G2M phase. These results suggest that ReIFN-γ and ReIFN-β used in combination were more effective in inhibiting the growth of human tumor cells and the proliferation of viruses than IFN used individually.
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