Marked improvement of thrombocytopenia in a murine model of idiopathic thrombocytopenic purpura by pegylated recombinant human megakaryocyte growth and development factor

• Published in: Experimental hematology Vol. 30; no. 10; pp. 1185 - 1192
• Main Authors: Shibuya, Kazunori, Kuwaki, Tomoaki, Tahara, Emiko, Yuki, Chizuru, Akahori, Hiromichi, Kato, Takashi, Miyazaki, Hiroshi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01-10-2002
• Subjects: Animals; Blood Platelets - drug effects; Blood Platelets - physiology; Crosses, Genetic; Disease Models, Animal; Humans; Male; Mice; Mice, Inbred Strains; Platelet Count; Polyethylene Glycols; Purpura, Thrombocytopenic, Idiopathic - blood; Purpura, Thrombocytopenic, Idiopathic - drug therapy; Purpura, Thrombocytopenic, Idiopathic - immunology; Recombinant Proteins - therapeutic use; Splenectomy; Thrombopoietin - therapeutic use; Time Factors
• ISSN: 0301-472X; 1873-2399
• DOI: 10.1016/S0301-472X(02)00898-6

We examined the stimulatory effect of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on platelet production in male (NZW × BXSB) F
l (W/B F
1) mice, a murine model of idiopathic thrombocytopenic purpura.
A cohort of 19- to 25-week-old, severely thrombocytopenic male W/B F
1 mice were given PEG-rHuMGDF at different dosing schedules. Before and at various times after therapy, platelet counts, reticulated platelets, platelet lifespan, and levels of platelet-associated immunoglobulin G were measured. Analysis of megakaryocytic cells was performed.
Treatment of male W/B F
1 mice with PEG-rHuMGDF (30 μg/kg/day) three times per week for several weeks resulted in sustained thrombocytosis, accompanied by increased megakaryocytopoiesis in both the bone marrow and spleen. The degree of the platelet response to PEG-rHuMGDF varied between individual mice, likely reflecting the heterogeneity of the disease. Production of new platelets in response to PEG-rHuMGDF was manifested by an increase in reticulated platelets. Levels of platelet-associated immunoglobulin G decreased inversely during periods of thrombocytosis. PEG-rHuMGDF therapy also improved thrombocytopenia in male W/B F
1 mice refractory to splenectomy. Platelet lifespan was not affected by PEG-rHuMGDF. Male W/B F
1 mice treated with pegylated murine MGDF, a homologue of PEG-rHuMGDF, had persistent thrombocytosis for at least 7 months, suggesting that antiplatelet antibody production was not enhanced.
PEG-rHuMGDF therapy potently stimulated platelet production, effectively ameliorating thrombocytopenia in a murine model of idiopathic thrombocytopenic purpura.