Prostaglandin E2 Promotes Recovery of Thymus in Survivors of the Hematopoietic Acute Radiation Syndrome (H-ARS)

Abstract We have previously developed a murine model of the hematopoietic acute radiation syndrome [H-ARS, total body irradiated (TBI)] and delayed effects of acute radiation exposure (DEARE) for efficacy testing of potential medical countermeasures (MCM) against these two syndromes. Using this model, we have previously reported that prophylactic use of 16,16 dimethyl-prostaglandin E2 (dmPGE2), a long-acting formulation of PGE, before irradiation significantly increases 30-day survival rate. The current study investigated the effects of the prophylactic use of dmPGE2 with or without therapeutic use of dmPGE2 in survivors on long-term thymus recovery in H-ARS survivors at 6 and 12-months post-LD70/30 (872cGy, 137Cs, 95.2±4.8 cGy/min). Mice were irradiated at 12 weeks of age and then injected subcutaneously with dmPGE2 (1 dose of 35 ug dmPGE2/mouse) or vehicle (Veh; ethanol/PBS solution) at 30“ or -1hr pre-TBI. Survivors were injected monthly with dmPGE2 or Veh and then analyzed for evidence of thymic reconstitution at 6 and 12 months.post-TBI. The three test groups were: prophylactic dmPGE2 + monthly dmPGE2 (PP), prophylactic dmPGE2 + monthly Veh (PV), and prophylactic Veh + monthly Veh (VV), n = 3-6 mice/group. Thymus weight and cellularity of mice in the dmPGE groups, PV and PP, were increased compared to Veh both at 6-months and 12-months post-TBI (p Disclosures No relevant conflicts of interest to declare.