Thrombopoietic activity of recombinant human interleukin-11 in nonhuman primates with ACNU-induced thrombocytopenia

The effect of recombinant human interleukin-11 (rHuIL-11) on myelosuppressi ve nimustine (ACNU)-induced thrombocytopenia was assessed in nonhuman prima tes. A single intravenous (i.v.) injection of ACNU (15 mg/kg) was administe red to cynomolgus monkeys on day 0. rHuIL-11 (100 mu g/kg/day) or the vehic le was given subcutaneously (s.c.) from day 1 to day 21. In monkeys receivi ng ACNU, the circulating platelet count decreased to a low of 42 +/- 6 x 10 (9)/L by day 21 but returned to pretreatment levels (375 +/- 48 x 10(9)/L) on day 30. Administration of rHuIL-11 prevented severe thrombocytopenia; th e platelet count fell only to 138 +/- 23 x 10(9)/L on day 18, and platelet recovery was faster (458 +/- 91 x 10(9)/L by day 27) compared with that of the control animals. The size of bone marrow megakaryocytes from rHuIL-11-t reated animals was larger than that of the controls, indicating that rHuIL- 11 stimulated megakaryopoiesis in a myelosuppressive condition. Treatment w ith ACNU also caused leukopenia and moderate anemia. rHuIL-11 transiently a nd slightly decreased the white blood cell (WBC) and red blood cell (RBC) c ounts. Conversely, rHuIL-11 accelerated recovery of RBC count in the late a dministration period. These results support the assertion that rHuIL-11 may be an important therapeutic agent for reducing the severity and duration o f thrombocytopenia following cancer chemotherapy.