Kinetic analysis of megakaryopoiesis induced by recombinant human interleukin 11 in myelosuppressed mice

Recombinant human interleukin 11 (rhIL-11) has previously been shown to ame liorate thrombocytopenia in several animal models. To elucidate the mechani sms involved in rhIL-11-induced hematopoiesis, a kinetic analysis of megaka ryopoiesis was performed in mitomycin C (MMC)-induced myelosuppressive mice . Mice intravenously injected with MMC (2 mg/kg) for two consecutive days f rom day - 1 developed severe thrombocytopenia with a nadir of platelet coun ts at 24 x 10(4)/mul on day 12 and neutropenia, Treatment with rhIL-11 (500 mug/kg/day) from day 1 to 21 significantly ameliorated the degree and dura tion of thrombocytopenia and enhanced the platelet recovery, and also enhan ced the recovery from neutropenia. In MMC-treated mice, the decreases in bo ne marrow megakaryocyte progenitors and megakaryocyte counts preceded the d ecrease in platelet counts by MMC treatment. RhIL-11 induced an increase in the number of megakaryocyte progenitors from day 4 to 14, followed by an i ncrease in the megakaryocytes by day 20. There was a ploidy shift in megaka ryocytes towards lower ploidy cells by day 9 in myelosuppressed mice. RhIL- 11 caused a shift towards a higher ploidy with 32 and 64N on day 4, and 32N on day 14. These results suggest that rhIL-11 ameliorates the thrombocytop enia via the stimulation of both the maturation and commitment followed by the proliferation of megakaryocytic cells, (C) 2001 Academic Press.