Administration of Recombinant Human Thrombopoietin Soon after Irradiation Promotes Survival and Stimulates Hematopoietic Recovery in a Nonhuman Primate Model of Radiation-Induced Severe Acute Radiation Syndrome

Abstract

Accidental or intentional irradiation causes incidents involving acute radiation syndrome (ARS) victims. Thus, it is urgent to search for effective radioprotectors with no or low toxicity. Recombinant human thrombopoietin (rhTPO) is a megakaryocyte colony-stimulating factor. We have demonstrated previously that early administration of rhTPO soon after irradiation promotes survival of lethal dose irradiated mice. To evaluate the therapeutic effect of rhTPO short-term injection soon after radiation in nonhuman primates exposed to a high dose of gamma ray, rhesus monkeys received subcutaneously of early rhTPO 10 μg/kg injection at 0.5 and 24 h after or WR2721 30 mg/kg intramuscularly administration at 0.5 h before total body irradiated (TBI) with a 7 Gy gamma dose. Survival was monitored and hematopoiesis was evaluated at 40 d following early treatment. rhTPO short-term early injection (0.5 and 24 h) after 7 Gy TBI induced 100.0% survival versus 33.3% in irradiated controls, while 83.3% in WR2721 protected monkeys. rhTPO early treatment significantly promoted hematopoiesis recovery and apparently improved the quality of life, and additionally simplified supportive care in ARS rhesus monkeys. According to the survival and hematopoiesis of irradiated nonhuman primates, radioprotection of rhTPO short-term injection soon after TBI is better than WR2721 administration at 0.5 h before TBI. Thus short-term injection of rhTPO soon after irradiation might be chosen as a first-line therapeutic strategy in the treatment of accidental acute radiation victims.