RADIOPROTECTION OF HEMATOPOIETIC STEM-CELLS BY INTERLEUKIN-1

Radioprotective agents such as interleukin-l (IL-1) and tumor necrosis factor (TNF-alpha), when given prior to irradiation, protect animals from radiation damage. However, in vivo administration of these cytoki nes does not allow one to determine whether the protective effects act directly on the hematopoietic system. In the present study, we subjec ted male bone marrow cells to in vitro treatment with IL-1 prior to ir radiation and bone marrow transplantation. We found that male bone mar row cells pretreated with IL-1 prior to irradiation increased the surv ival of irradiated female recipient mice when compared with nontreated irradiated marrow cells. In addition, irradiated female recipients th at received IL-l-pretreated male donor bone marrow cells displayed an increased presence of male donor cells in their bone marrow, spleen, a nd thymus for up to 3 months posttransplant. Furthermore, serial trans plantation studies revealed that male cells could only be detected in tertiary female recipients who received bone marrow from mice transpla nted with IL-l-treated cells. These results indicate that IL-1 pretrea tment protects both short-term and long-term repopulating stem cells f rom an irradiation insult and that these cells are capable of reconsti tuting the myeloid and lymphoid organs of recipient mice.