Previous studies have evaluated the effects of hyperthermia on the antiproliferative activity of interferon. The activities of all three types of interferon have been shown to be synergistically enhanced by hyperthermic conditions. Further, the antiproliferative activity of interferon has been shown to be synergistically enhanced by combinations of gamma-plus alpha- or beta-interferon. The question remained whether combining these two methods of enhancing interferon activity would lead to an even higher level of enhancement of antiproliferative activity or to an antagonism of their separate effects. To address this question, mouse B-16 melanoma cells were cloned at 37.3 degrees C and at 39.4 degrees C in the presence of various combinations of murine alpha/beta- and gamma-interferon. Potentiation of interferon's antiproliferative activity by combination interferon treatment was found to occur at both temperatures. Moreover, the level of potentiation was synergistically enhanced by hyperthermic conditions. The results suggest that a combined treatment regimen of hyperthermia and combination interferon therapy (gamma- plus alpha- or beta-interferon) may provide a highly potent antitumor effect.
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