Thrombopoietic Activity of Recombinant Human Interleukin-11 in Nonhuman Primates with ACNU-Induced Thrombocytopenia

Abstract

The effect of recombinant human interleukin-11 (rHuIL-11) on myelosuppressive nimustine (ACNU)-induced thrombocytopenia was assessed in nonhuman primates. A single intravenous (i.v.) injection of ACNU (15 mg/kg) was administered to cynomolgus monkeys on day 0. rHuIL-11 (100 mu g/kg/day) or the vehicle was given subcutaneously (s.c.) from day 1 to day 21. In monkeys receiving ACNU, the circulating platelet count decreased to a low of 42 ± 6 X 109/L by day 21 but returned to pretreatment levels (375 ± 48 X 109/L) on day 30. Administration of rHuIL-11 prevented severe thrombocytopenia; the platelet count fell only to 138 ± 23 X 109/L on day 18, and platelet recovery was faster (458 ± 91 X 109/L by day 27) compared with that of the control animals. The size of bone marrow megakaryocytes from rHuIL-11-treated animals was larger than that of the controls, indicating that rHuIL-11 stimulated megakaryopoiesis in a myelosuppressive condition. Treatment with ACNU also caused leukopenia and moderate anemia. rHuIL-11 transiently and slightly decreased the white blood cell (WBC) and red blood cell (RBC) counts. Conversely, rHuIL-11 accelerated recovery of RBC count in the late administration period. These results support the assertion that rHuIL-11 may be an important therapeutic agent for reducing the severity and duration of thrombocytopenia following cancer chemotherapy.