Synergistic effect of interferon-gamma and tumor necrosis factor-alpha on antiviral activity and (2'-5') oligo (A) synthetase induction in a myelomonocytic cell line.

TNF was not observed to have an antiviral effect on either HL60 or U937 cells. However, it did significantly enhance interferon (IFN)-gamma-mediated antiviral activity in U937 cells. Treatment of U937 cells with IFN-gamma enhanced (2'-5') oligo (A) synthetase activity (2.5-fold) but treatment with TNF did not. Combined treatment with TNF-alpha + IFN-gamma increased this activity dramatically (20-40-fold). This increase correlated with the very large increase in the (2'-5') oligo (A) synthetase mRNA level in U937 cells. No such effects were observed in HL60 cells. Furthermore, binding studies and cross-linking analysis showed that IFN-gamma modulated TNF-alpha receptors in U937 cells without altering their properties, but did not do so in HL60 cells.