Hematopoietic cytokines enhance survival of SCID mice undergoing high-dose irradiation.

We have investigated the effect of hematopoietic cytokines on the survival of severe combined immune-deficient (SCID) mice that received a high dose of radiation. In this study, female SCID mice were irradiated at doses ranging from 500 to 600 cGy and then transplanted with 2 x 10(6) male Balb/c marrow cells. Groups of transplant recipients received stem cell factor (SCF), interleukin-1 (IL-1), and IL-3, alone or in combination, once daily for 5 days immediately after irradiation. Control posttransplant SCID recipients did not survive more than 2 weeks after irradiation with the dose over 500 cGy. SCF alone did not enhance survival, and treatment with IL-1 or IL-3 had very limited capacity to improve survival. IL-1 plus IL-3 has some radioprotective effect on SCID recipients, but the strongest synergistic radioprotective effect was observed in mice treated with a combination of SCF, IL-1, and IL-3. These mice survived for more than 4 months after an irradiation dose up to 600 cGy. We also examined the origin of hematopoietic stem cells in transplant recipients. Bone marrow cells were obtained from the SCID mice treated with a combination of cytokines at 2 and 4 months after transplant with male Balb/c marrow cells and irradiation with 600 cGy. These marrow cells were then transplanted into secondary lethally irradiated female Balb/c recipients. Twelve-day spleen colonies (CFU-S) were analyzed by amplification of the Y-chromosome sequence of the sex-determining region by polymerase chain reaction (PCR). All spleen colonies were of donor origin, indicating that the SCID recipients were fully reconstituted by donor cells. The results suggest that SCF, synergistic with IL-1 and IL-3, protects SCID mice from lethal doses of radiation and allows complete long-term engraftment of SCID recipients.