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Synergistic Cytotoxic Effects of Recombinant Human Tumor Necrosis Factor, Interferons, and Heat-Stress¹

INSERM U 43, Hôpital Saint-Vincent de Paul, 74 Avenue Denfert-Rochereau, 75014 Paris, France

A synergistic increase in the cytotoxic effects of recombinant human tumor necrosis factor (TNF-), interferons (IFN-, IFN-ß, and IFN-) and heat-stress was demonstrated in vitro. The toxicity of these agents was assessed in the human cervical carcinoma HeLa cell line: the toxic effect was greatly increased when cells pretreated with IFNs or TNF were submitted to a 1-h heat-shock at 45°C. Moreover if the heat-stress followed simultaneous treatment with both cytokines, a synergistic effect between these treatments could be observed. The same observations were made for two other transformed cell lines: the oral epidermoid carcinoma KB cells and the hepatocarcinoma PLC/PRF/5 cells. In contrast, the survival of normal cells (normal foetal lung MRC5 cells and foreskin F 7000 fibroblasts) was only slightly decreased by such treatments. These results suggest that combining a heat-stress with cytokines treatment might be one way of enhancing the sensitivity of cancer cells to the growth inhibitory effects of the individual cytokines.

¹ This work was supported in part by Grant 6308 from the Association pour la Recherche sur le Cancer, Villejuif.

² To whom requests for reprints should be addressed.

Received 3/28/89. Revised 7/ 6/89. Accepted 7/20/89.

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