Radioprotection of haemopoietic stem cells by a single injection of bacterial lysate — IRS-19 administered to mice before or after irradiation

Abstract

Data in this report describes the effect of a single injection of bacterial lysate IRS-19 prior to irradiation of C57Bl/6 mice on recovery of colony-forming cells (CFC) after sublethal and lethal doses of radiation. The injection of IRS-19 promoted an earlier recovery of colony-forming cells in the bone marrow and spleen. For example, 5 and 9 days after 7.5 Gy irradiation, the number of CFU-S per femur was approximately 1.7–2.3-fold higher in IRS-19-injected mice than in saline-injected mice. Also, pretreatment of mice with IRS-19 induced an increase in the number of endogenous haemopoietic stem cells (endoCFU-S). In the postradiation period (5–21 days) significantly increased bone marrow and spleen cellularity and accelerated myelopoietic regeneration (committed progenitor granulocyte-macrophage–colony-forming cells, GM–CFC) in the bone marrow and spleen compared with saline-treated controls. At the time of presumed irradiation, (i.e. 24 h after administration of the drug to the non-irradiated mice), there was no significant difference between the control mice and mice treated with IRS-19 in numbers of femoral and spleen GM–CFC. In contrast, the number of nucleated femoral cells decreased significantly in the group treated with IRS-19. Moreover, treatment with IRS-19 caused a sustained increase in serum colony-stimulating activity which was followed by an enhanced repopulation of GM–CFC in the femoral marrow and spleen. Administration of the agent 24 h prior to irradiation rather than postirradiation appeared most effective with respect to radioprotection. Intravenous rather than i.p. and p.o. was the most effective route of administration in the mouse. Furthermore, single, high-dose injection appeared to be more effective than repeated, lower dose injections. Results suggest that the radioprotective properties associated with the administration of IRS-19 are largely a consequence of the induction of haemopoietic colony-stimulating activities and potentially the activation and/or enhancement of cytokine cascades in the recipient animals. These changes may ultimately impact the cell cycle profile of the haemopoietic cells and therefore their ability to withstand and/or recover from radiation insult.