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Thrombopoietic Activity of Recombinant Human Interleukin 11 (rHuIL-11) in Normal and Myelosuppressed Nonhuman Primates

^a Genetics Institute, Inc., Cambridge, Massachusetts, USA;
^b Children's Hospital, Philadelphia, Pennsylvania, USA

Key Words. rHuIL-11 • Nonhuman primate • Megakaryocytopoiesis • Thrombopoiesis • Chemotherapy

Correspondence: Franklin J. Schlerman, Genetics Institute, 2 Burtt Road, Andover, MA 01810, USA.

We have extensively characterized the hematological response of normal and myelosuppressed nonhuman primates to treatment with recombinant human interleukin 11 (rHuIL-11) in vivo. In normal cynomolgus monkeys, rHuIL-11 significantly increased peripheral platelet counts when administered at doses of 10 µg/kg/day to 100 µg/kg/day either by constant i.v. infusion or s.c. injection. As few as four days of rHuIL-11 treatment were sufficient to increase peripheral platelet counts significantly. In addition, extending the treatment period enhanced both the magnitude and the duration of the response. Bone marrow megakaryocytes from animals treated with 100 µg/kg/day of rHuIL-11 were increased in size compared to controls and were ultrastructurally normal. A nonhuman primate myelosuppression model using carboplatin, which causes severe thrombocytopenia with platelet counts of 20 x 10³ platelets/µl, was developed. This novel model was used to evaluate the effectiveness of rHuIL-11 in platelet restoration. rHuIL-11, administered s.c. at a dose of 125 µg/kg/day either concurrently or following chemotherapy, prevented severe thrombocytopenia in addition to accelerating platelet recovery compared to control animals receiving no rHuIL-11. These data demonstrate that rHuIL-11 has potent in vivo thrombopoietic effects when administered to normal and myelosuppressed nonhuman primates, and that rHuIL-11 can be an important therapy to reduce the severity and duration of thrombocytopenia following chemotherapy.

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