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

Abstract
Recombinant human interleukin 11 (rhIL-11) has previously been shown to ameliorate thrombocytopenia in several animal models. To elucidate the mechanisms involved in rhIL-11-induced hematopoiesis, a kinetic analysis of megakaryopoiesis was performed in mitomycin C (MMC)-induced myelosuppressive mice. Mice intravenously injected with MMC (2 mg/kg) for two consecutive days from day -1 developed severe thrombocytopenia with a nadir of platelet counts at 24x10(4)/microl on day 12 and neutropenia. Treatment with rhIL-11 (500 microg/kg/day) from day 1 to 21 significantly ameliorated the degree and duration of thrombocytopenia and enhanced the platelet recovery, and also enhanced the recovery from neutropenia. In MMC-treated mice, the decreases in bone marrow megakaryocyte progenitors and megakaryocyte counts preceded the decrease 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 increase in the megakaryocytes by day 20. There was a ploidy shift in megakaryocytes 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 thrombocytopenia via the stimulation of both the maturation and commitment followed by the proliferation of megakaryocytic cells.
AuthorsM Saitoh, K Taguchi, K Momose, K Suga, Y Ogawa, S Yasuda, K Miyata
JournalCytokine (Cytokine) Vol. 13 Issue 5 Pg. 287-94 (Mar 07 2001) ISSN: 1043-4666 [Print] England
PMID11243707 (Publication Type: Journal Article)
Chemical References
  • Alkylating Agents
  • Immunosuppressive Agents
  • Interleukin-11
  • Nucleic Acid Synthesis Inhibitors
  • Recombinant Proteins
  • Mitomycin
Topics
  • Alkylating Agents (pharmacology)
  • Animals
  • Blood Platelets (metabolism)
  • Bone Marrow Cells (metabolism)
  • Cell Differentiation
  • Cell Division
  • Female
  • Femur (cytology)
  • Humans
  • Immunosuppressive Agents (pharmacology)
  • Interleukin-11 (pharmacology)
  • Kinetics
  • Megakaryocytes (cytology, drug effects, metabolism)
  • Mice
  • Mice, Inbred BALB C
  • Mitomycin (pharmacology)
  • Nucleic Acid Synthesis Inhibitors (pharmacology)
  • Ploidies
  • Recombinant Proteins (pharmacology)
  • Stem Cells
  • Thrombocytopenia (chemically induced)
  • Time Factors

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