title: Marked improvement of thrombocytopenia in a murine model of idiopathic thrombocytopenic purpura by pegylated recombinant human megakaryocyte growth and development factor.
abstract: OBJECTIVE
  We examined the stimulatory effect of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on platelet production in male (NZW x BXSB) F(l) (W/B F(1)) mice, a murine model of idiopathic thrombocytopenic purpura.
  
  
  METHODS
  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.
  
  
  RESULTS
  Treatment of male W/B F(1) mice with PEG-rHuMGDF (30 microg/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.
  
  
  CONCLUSIONS
  PEG-rHuMGDF therapy potently stimulated platelet production, effectively ameliorating thrombocytopenia in a murine model of idiopathic thrombocytopenic purpura.
authors.affiliation: Pharmaceutical Development Laboratory, Kirin Brewery Company, Ltd., Gunma, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Shibuya
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Kuwaki
authors.forename: Emiko
authors.initials: E
authors.lastname: Tahara
authors.forename: Chizuru
authors.initials: C
authors.lastname: Yuki
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Akahori
authors.forename: Takashi
authors.initials: T
authors.lastname: Kato
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyazaki
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010976:Platelet Count; D011092:Polyethylene Glycols; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D011994:Recombinant Proteins / Q000627:therapeutic use; D013156:Splenectomy; D013926:Thrombopoietin / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D013926:Thrombopoietin