Synergistic effects of cytokine and hyperthermia on cytotoxicity in HT-29 cells are not mediated by alteration of induced protein levels.

In this study, we investigated the mechanism of synergistic effects of cytokine and hyperthermia on cytotoxicity in HT-29. When cells were heated at 42 degrees C in the presence of recombinant human tumor necrosis factor (rhTNF-alpha), recombinant interferon-gamma (rhIFN-gamma), or in a combination of both, a synergistic increase in the cytotoxic effects of the respective drugs was observed. We hypothesized that alteration of cytokine or heat-induced polypeptides synthesis was responsible for a synergistic interaction between heat and cytokine. Five heat shock proteins (HSPs, M(r) 110,000, 100,000, 90,000, 70,000, and 28,000) were preferentially synthesized during chronic heating at 42 degrees C. In contrast, the synthesis of two proteins (M(r) 60,000 and 29,000) was induced by treatment with rhIFN-gamma (1,000 U/ml). Although the combination of chronic hyperthermia (42 degrees C) with TNF-alpha, IFN-gamma, or TNF-alpha + IFN-gamma increased cytotoxicity, alteration/induction of polypeptides was not correlated with the synergistical cytotoxic effects of cytokine and heat. Thus, the synergistic effects of cytokine and hyperthermia are not mediated through an induction of polypeptides.