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.
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Authors | M Saitoh, K Taguchi, K Momose, K Suga, Y Ogawa, S Yasuda, K Miyata |
Journal | Cytokine
(Cytokine)
Vol. 13
Issue 5
Pg. 287-94
(Mar 07 2001)
ISSN: 1043-4666 [Print] England |
PMID | 11243707
(Publication Type: Journal Article)
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Chemical References |
- Alkylating Agents
- Immunosuppressive Agents
- Interleukin-11
- Nucleic Acid Synthesis Inhibitors
- Recombinant Proteins
- Mitomycin
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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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