Recombinant tumor necrosis factor: its effect and its synergism with interferon-gamma on a variety of normal and transformed human cell lines.

Tumor Necrosis Factor (TNF), released by induced macrophages, causes tumor necrosis in animals, and preferentially kills transformed cells in vitro. Using pure, recombinant human TNF, we report here its cytotoxic action on several human transformed and non-transformed cell lines. Furthermore, remarkable synergism between TNF and interferon-gamma (IFN-gamma) was observed in a large number of human cell lines, especially breast, cervix and colon carcinomas. Some other human cell lines, not sensitive to TNF alone, became highly sensitive when IFN-gamma was present as well. We could not demonstrate a synergism between TNF and IFN-gamma on any of the lymphoma/leukemia cell lines tested. All normal human, non-transformed diploid cell lines were insensitive to TNF even in the presence of IFN-gamma. This study also confirms the observation that inhibition of protein synthesis by metabolic drugs (e.g. actinomycin D) remarkably enhances the sensitivity of several target cell lines to cytolysis by TNF.