THROMBOPOIETIN ACCELERATES PLATELET, RED-BLOOD-CELL, AND NEUTROPHIL RECOVERY IN MYELOSUPPRESSED MICE

The recent cloning of thrombopoietin (TPO) has allowed us to study its in vivo effects in normal and myelosuppressed mice. Normal Balb/c mic e were treated with recombinant human TPO (hTPO) at doses ranging from 1 to 20 kU for 7 days, and complete blood counts (CBCs) and the numbe r of megakaryocytes in the bone marrow were determined. Platelet count s were increased starting on day 5 after mice were treated with hTPO. Platelet counts reached a peak between days 8 and 11 and returned to b aseline between days 16 and 20. hTPO treatment increased the number of megakaryocytes in the bone marrow starting on day 3. In normal mice, hTPO treatment did not affect red or white blood cell (RBC or WBC) cou nts. To test the effects of hTPO in myelosuppressed mice, Balb/c mice were irradiated with 350 cGy total-body irradiation and dosed with 1.2 mg carboplatin, resulting in severe and prolonged thrombocytopenia, a nemia, and neutropenia. Treatment with 5-20 kU hTPO for 7 days acceler ated the recovery of platelet, RBC, and neutrophil counts in myelosupp ressed mice and also significantly improved their nadirs. In addition, bone marrow megakaryocyte numbers recovered 11 days earlier and retic ulocyte counts recovered 10 days earlier in hTPO-treated myelosuppress ed mice than in controls. These results indicate that TPO can improve hematopoietic recovery in myelosuppressed mice, affecting multiple cel l lineages.