Interleukin-1 alpha protects against the toxicity associated with combined radiation and drug therapy

A dose of total body irradiation sufficient to cause 70% mortality within 30 days (9.5 Gy) and maximally tolerated doses of either adriamycin (10 mg/kg) or cis-dichlorodiammine platinum (8 mg/kg) were administered to C57B1/6 mice and animal survival used as an index of toxicity. Whereas the nature of the toxicity resulting from the radiation alone was hematopoietic, the addition of either drug to the total body irradiation resulted in a pattern of animal death more consistent with that of gastrointestinal toxicity (100% dead within 7 days). However, if the radiation was delivered as a regional abdominal exposure, rather than total body, the gastrointestinal death observed following the combination of total body irradiation drug was not observed. The administration of 2.5 x 10(5) U IL-1 v24 hr prior to total body irradiation demonstrated significant protection against this dose of radiation (90% survival vs 30% survival). Similar protection was also observed when the IL-1 was administered 24 hr prior to the combination of total body irradiation with either drug. While these observations suggested that the IL-1 was protecting against gastrointestinal toxicity, subsequent studies demonstrated that IL-1, in addition to accelerating hematopoietic recovery following radiation insult, was equally effective in advancing the repopulation of the stem cell (CFU-GEMM) and progenitor cell (CFU-M and CFU-GM) compartments following drug treatment. Collectively, the data from these studies demonstrate that the lethal effects resulting from combined total body irradiation + drug treatment contain both a gastrointestinal and a hematopoietic component.