Marked improvement of thrombocytopenia in a murine model of idiopathic thrombocytopenic purpura by pegylated recombinant human megakaryocyte growth and development factor.
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.
Shibuya
Kazunori
K
Pharmaceutical Development Laboratory, Kirin Brewery Company, Ltd., Gunma, Japan.
Kuwaki
Tomoaki
T
Tahara
Emiko
E
Yuki
Chizuru
C
Akahori
Hiromichi
H
Kato
Takashi
T
Miyazaki
Hiroshi
H
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
D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D013926:Thrombopoietin