Synergistic anticellular and antiviral activities of human recombinant interferon-gamma and -beta

The synergism of anticellular and antiviral activities of recombinant human interferon-gamma (ReIFN-gamma) and recombinant human interferon-beta (ReIFN-beta) 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-beta occurred earlier than that of ReIFN-gamma. Significant synergism was detected in the anticellular activity of both IFNs when growth curves and isobolograms were examined. A difference between ReIFN-gamma and ReIFN-beta was also detected in antiviral activity. The antiviral activity of ReIFN-gamma against vesicular stomatitis virus (VSV) was significantly weaker than that of ReIFN-beta, even though both IFNs exhibited almost equivalent antiviral activities against Sindbis virus. However, ReIFN-gamma and ReIFN-beta 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-gamma alone, ReIFN-beta alone, or ReIFN-gamma and ReIFN-beta in combination. ReIFN-beta induced a prolongation or accumulation of S phase, whereas the effect of ReIFN-gamma was cycle-nonspecific. The combination of ReIFN-gamma and ReIFN-beta induced a decrease of G1 phase and an increase of G2M phase. These results suggest that ReIFN-gamma and ReIFN-beta used in combination were more effective in inhibiting the growth of human tumor cells and the proliferation of viruses than IFN used individually.