Abstract
Infection of mice with the murine leukemia virus (LP-BM5) was evaluated as a model for the thrombocytopenia of HIV/AIDS. Percent 35S incorporation into platelets, platelet size, platelet count, platelet-associated immunoglobulins (PAIgG), and megakaryocyte size and number were evaluated over a period of 3-9 weeks postinfection (PI). Thrombopoietin from human embryonic kidney cells was administered to mice 9 weeks PI, and similar indices of platelet production were measured 2, 3, and 4 days after treatment with a biological preparation of thrombopoietin (thrombocytopoiesis-stimulating factor, or TSF). Platelet counts decreased in a time-dependent fashion (p = 0.0006) following infection, reaching a nadir at 8 weeks PI (82% of control values). Percent 35S incorporation into platelets also decreased over the 9-week period (p = 0.0001), falling to 63% of control values by week 9. Additionally, platelet volume increased in a linear fashion (p = 0.01), rising to 105% of control values by week 9. No changes in PAIgG were noted over the 9-week period. Megakaryocyte numbers in the femoral marrow were decreased at 8 weeks PI (p = 0.02, 78% of control values), while increased mean megakaryocyte size (p = 0.007,116% of controls) was noted in the same animals. Increased numbers of naked megakaryocyte nuclei were observed at 3 weeks PI (p < 0.05, 208% of control values). Administration of 2 U/mouse of a highly purified preparation of TSF to virus-infected, thrombocytopenic mice resulted in increased thrombocytopoiesis, as compared to human serum albumin-treated, virusinfected controls. Specifically, platelet counts increased at 3 days following TSF administration (p < 0.01, 121% of control mice), whereas both 35S incorporation into platelets and platelet volume increased 2 days after TSF administration (p < 0.005,145% of control values and p < 0.01,110% of control values, respectively). Infection with MuLV results in thrombocytopenia in C57BL/6 mice, and the mechanism of this thrombocytopenia is by decreased production of platelets with no evidence of a peripheral immunodestructive mechanism for thrombocytopenia. Therefore, MAIDS is a reasonable model for the portion of HI V-related thrombocytopenia attributable to decreased marrow production of platelets, but does not appear to be an appropriate model for the immune-mediated mechanisms of HRT. Additionally, thrombopoietin holds promise as a specific treatment for HIV-related thrombocytopenia.
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