Potentiation of tumor necrosis factor-mediated cytotoxicity on human myeloid cell lines: effects of interferons versus dimethylsulphoxide.

After prolonged incubation times of 72 h IFN alpha 2a and IFN beta 1 significantly reduced cell growth in the myelomonocytic U937 and THP1 cell lines. IFN gamma showed only slight growth inhibitory activities. IFN activities were potentiated by the highly polar differentiation inducer dimethylsulphoxide, which is similar to our previous study on tumor necrosis factor (TNF). However, in contrast with TNF, none of the interferon types induced cell cytotoxicity or DNA fragmentation. Like DMSO, all interferons potentiated TNF-induced cytotoxicity, IFN beta 1 and IFN gamma being the most potent in this respect. When applied together, DMSO and IFN gamma enhanced TNF-mediated cell lysis in either an additive (in the case of U937, THP1, HL60 cells) or a synergistic (in the case of KG1) manner, suggesting that the mechanisms of the potentiating activity of DMSO and IFN gamma are different. The potential role of the simultaneous use of DMSO-related molecules, and TNF and/or IFN in leukemic cancer chemotherapy is discussed.