Therapeutic effect of Halofuginone on ITP mice by regulating the differentiation of Th cell subsets

Abstract

The aim of the present study was to investigate the therapeutic effect of halofuginone (HF) in the treatment of idiopathic thrombocytopenic purpura (ITP) and explore the underlying mechanism. Sixty ITP mice were divided into four groups including control group, low dose group (25 mg/kg HF), medium dose group (50 mg/kg HF), and high dose group (100 mg/kg HF). Corresponding dose of HF was administrated by gavage daily in HF groups for 7 days, and the same volume of saline was given in control group. Platelet counts were 28.87 ± 3.91 × 10(9)/L, 57.13 ± 2.75 × 10(9)/L, 86.73 ± 3.06 × 10(9)/L and 89.73 ± 2.84 × 10(9)/L in control group, low dose group, medium dose group, and high dose group respectively, on day 7 after intragastrically administration of HF or saline. Compared with control group, three HF groups showed significantly increased levels of INF-γ and IL-2 (all P < 0.05), and significantly decreased concentrations of IL-4 and IL-10(all P < 0.05). The expression of T-bet mRNA increased and the expression of GATA-3 mRNA decreased (all P < 0.05) in ITP mice after intragastric administration with different dose of HF. HF significantly recovered peripheral platelet counts in ITP mice through promoting Th1 cell differentiation and attenuating Th2 differentiation in ITP mice.