Antitumor effect of interleukin 1 alpha in combination with hyperthermia.

The combined effects of interleukin-1 alpha (IL-1 alpha) and hyperthermia on SCK tumors grown in the legs of A/J mice were investigated. When the host mice were given i.p. injections of 25 micrograms/kg IL-1 alpha, the tumor blood perfusion, as measured with the 86Rb uptake method, significantly declined, reaching minimum blood perfusion in 3-5 h. Although the tumor blood perfusion started to rise thereafter, the recovery was still incomplete 1 day later. Hyperthermia at 42.5 degrees C or 43.5 degrees C for 1 h also caused a marked decline in tumor blood perfusion. When the tumors were heated 5 h after an i.p. injection of IL-1 alpha at 25 micrograms/kg, at which time the tumor blood perfusion was low, the tumor blood perfusion decreased further. The heating of tumors at 42.5 degrees C or 43 degrees C for 1 h significantly reduced the clonogenic cell number in the tumors, delayed the tumor growth, and prolonged the survival time of host animals. The antitumor effect of 25 micrograms/kg IL-1 alpha alone, as judged from the clonogenic cell number, tumor growth delay, and host survival, was smaller than that of hyperthermia. When the host mice were treated with IL-1 alpha and the tumors were heated 5 h later, the decline in the clonogenic tumor cell number, tumor growth delay, and prolongation of host survival were significantly greater than those produced by either treatment alone. It was concluded that the prior reduction of blood perfusion by IL-1 alpha potentiated the antitumor effect of subsequent heatings.