Influences of High-Dose Dexamethasone on Regulatory T Cells, Transforming Growth Factor-β1 and Interleukin-10 of Patients with Chronic ITP.

Immune thrombocytopenic purpura (ITP) is an autoimmune disorder and high-dose dexamethasone (HD-DXM) has been used as a first-line therapy for patients with ITP. However, little is known about the role of CD4⁺CD25 ⁺ regulatory T (Treg) cells, interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1) in the pathogenesis of chronic ITP and the effects of HD-DXM on them contained Treg cells, IL-10 and TGF-β1. In this study, we investigated the expressions of Treg cells, IL-10 and TGF-β1 in 26 untreated adult patients with chronic ITP. All patients had thrombocytopenia (platelet count <50 × 10⁹/L) for more than 6 months. We also observed short time changes of Treg cells, IL-10 and TGF-β1 after treatment with HD-DXM in these patients. The results showed that a good initial response to HD-DXM occurred in 24 of the 26 patients with chronic ITP (92.3%): the mean platelet count was (84.9±30.4)×10⁹/L [range, (20∼150) ×10⁹/L] one week after the initiation of treatment. The proportion of CD4⁺CD25⁺ T cells in the peripheral blood of patients with chronic ITP was significantly higher than that in normal controls(P<0.001); there was no significant difference in the percentage of CD4⁺CD25^high T cells between patients and controls ( P=0.317); but the number of CD₄⁺ F_OXP3⁺ T cells in patients was significantly lower than that in controls (P<0.001). After 4-days treatment with HD-DXM, the numbers of CD₄⁺ CD25⁺ T cells (P<0.001), CD₄⁺CD₂₅^high T cells ( P<0.001), and CD4⁺F_OXP3⁺ T cells ( P<0.001) in patients were all significantly increased. In the serum of chronic ITP patients, the expression level of TGF-β1 was lower than that of healthy controls (P<0.0001) and HD-DXM could significantly increase it; there was no significant difference in the expression level of IL-10 between patients and controls ( P>0.05) and there was no remarkable change of IL-10 in patients after HD-DXM treatment (P>0.05). The mRNA levels of Foxp3 and TGF-β1 gene in patients were lower than those of controls (P<0.05 and P<0.05); HD-DXM administration significantly increased the expressions of Foxp3 and TGF-β1 gene(P<0.05 and P<0.0001), which were even higher than those of controls(P<0.05 and P<0.05); There was a positive correlation between the Foxp3 mRNA expression and TGF-β1 after treatment with HD-DXM (r =0.403, P=0.041). These results suggest that Foxp3 and TGF-β1 gene are deficient in chronic ITP and the immunosuppressive therapy of glucocorticoids could improve the expression levels of these genes.