INTERLEUKIN-1 MODIFICATION OF THE EFFECTS OF CYCLOPHOSPHAMIDE AND FRACTIONATED-IRRADIATION

Studies were performed to determine whether recombinant human interluekin-1 (IL-1) modifies the tumor cytotoxicity of cyclophosphamide (CY) combined with fractionated X-irradiation. RIF-1 tumors were implanted intradermally in C3H/Km mice and therapeutic effect was evaluated by the regrowth delay method, that is, the time for treated tumors to grow to 3 times their volume at the start of treatment relative to that for untreated tumors. A single intraperitoneal treatment of 15-mu-g/kg IL-1 given 24 hr after 100 or 200 mg/kg CY and immediately before the first of 5 daily fractionated treatments of 1-4 Gy increased tumor growth delay beyond that produced by CY and irradiation without the IL-1. However, the IL-1 given with either CY or fractionated irradiation did not extend the time for tumor regrowth beyond that produced by the agents themselves. Thus, while CY and fraction ated irradiation together produce a greater than additive effect, IL-1 seems to extend this phenomenon. From these findings, it appears that IL-1 enhances the cytotoxic effects of CY and X ray against tumors, an effect th at would have considerable practical significance in the light of the prote ctive effects shown elsewhere for the same lymphokine on normal tissues.