Effect and mechanism of low-dose chidamide on the treatment of primary immune thrombocytopenia
10.3760/cma.j.issn.0253-2727.2020.04.006
- VernacularTitle:低剂量西达本胺治疗原发免疫性血小板减少症及其作用机制研究
- Author:
Hongyu ZHAO
1
;
Daqi LI
;
Juan WANG
;
Yu HOU
;
Lu SUN
;
Jun PENG
;
Ming HOU
Author Information
1. 山东第一医科大学附属济南市中心医院血液科，济南 250013
- Keywords:
Chidamide;
Immune thrombocytopenia;
Regulatory T cell;
Immunological tolerance
- From:
Chinese Journal of Hematology
2020;41(4):292-296
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the effect and mechanism of low-dose chidamide on the treatment of primary immune thrombocytopenia (ITP) .Methods:Passive ITP animal model and active ITP animal model were established by C57BL/6J mice. Different doses of chidamide (0, 0.01, 0.1, 0.5, and 5 mg/kg) were orally administrated twice a week for 120 hours in passive ITP mice. Secondly, low-dose chidamine (0.1 mg/kg) was given intragastrically administrated twice a week in active ITP mice. The platelet counts in the peripheral blood before and after treatment were detected. Four weeks later, mice were executed to prepare splenocyte suspension; natural regulatory T cells (CD4 +CD25 +Foxp3 + nTreg cells) in splenocyte suspension were detected by flow cytometry. Serum IL-6 was measured by ELISA. Peripheral blood mononuclear cells from ITP patients were co-cultured with low-dose chidamide in vitro. After incubation for 72 hours, CD4 +CD25 +Foxp3 + Treg cells of mononuclear cells was detected. CD4 +CD25 + Treg cells and CD4 +CD25 - effector T cells were separated by immunomagnetic beads. The Treg cells and effector T cells were co cultured in a ratio of 1∶4, and treated with low-dose chidamide. The proliferation of effector T cells was detected. Results:Chidamide with low dose (0.1 mg/kg) significantly improved platelet counts in passive ITP mouse model, as well as in the ITP active mouse model and reduced the mortality related to bleeding. Low-dose chidamide significantly increased the number and proportion of nTreg cells in mouse splenocytes, and decreased serum IL-6 level in active ITP mice. In ITP patients, low-dose chidamide also significantly expanded Treg cells in the PBMC culture system. Besides, the proliferation of effector T cells was suppressed.Conclusion:Low-dose chidamide enhances the proliferation of CD4 +CD25 +Foxp3 + regulatory T cells to mediate immunosuppressive function. Serum IL-6 is inhibited for further immune tolerance. In vivo animal study suggestes that low-dose chidamide has a novel therapeutic effect on ITP.
