Studies were performed to determine whether recombinant human
interleukin-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 micrograms/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 fractionated 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 that would have considerable practical significance in the light of the protective effects shown elsewhere for the same lymphokine on normal tissues.