Therapeutic effect of TPO and G-CSF on acute radiation sickness of monkeys

Objective: The author describes the therapeutic effects of recombinant human thrombopoietin (rhTPO) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) on acute radiation sickness in monkeys. Methods: rhTPO(10μg·kg-1·d-1, sc, on days 1-21 after TBI) or/and rhG-CSF (5μg·kg-1·d-1, sc, on days 1-21 after TBI) were administered to rhesus monkeys with 5.0 Gy X-irradiation. Results: rhTPO promoted platelet and reticulocyte recovery, resulting in less profound nadirs and a rapid recovery to normal levels. Platelet transfusion were not required in contrast to controls, while hemoglobin levels stabilized rapidly. TPO treatment did not influence neutrophil counts, rhG-CSF stimulated neutrophil regeneration and had no effect on platelet levels. Simultaneous administration of rhTPO and rhG-GSF were as effective as rhTPO alone in preventing thrombopenia, although the platelet level did not rise to the supranormal level seen with TPO alone. The neutrophils were greatly augmented in number, compared to G-CSF treatment alone, resulting in a less profound nadir and much earlier recovery, which was similarly observed for monocytes, CD11b+, CD16+ and CD56+ cell reconstitution. Conclusion: These data show that rhTPO and rhG-GSF are potent stimulators of hematopoiesis in monkeys with radiation sickness