Open AccessEffect of arsenic trioxide on the Tregs ratio and the levels of IFN-γ, IL-4, IL-17 and TGF-β1 in the peripheral blood of severe aplastic anemia patients
Author(s) -
Juanjuan Zhao,
Yongping Song,
Lina Liu,
Shiwei Yang,
Baijun Fang
Publication year - 2020
Publication title -
medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 148
eISSN - 1536-5964
pISSN - 0025-7974
DOI - 10.1097/md.0000000000020630
Subject(s) - medicine , arsenic trioxide , peripheral blood mononuclear cell , aplastic anemia , foxp3 , immunology , anemia , regulatory t cell , interleukin , gastroenterology , cytokine , t cell , apoptosis , il 2 receptor , immune system , in vitro , bone marrow , biochemistry , chemistry
Previous studies have suggested that the anticancer agent, arsenic trioxide (ATO), could attenuate T cell mediated immunity by not only inhibiting the proliferative response of T cells but by also increasing the frequency of regulatory T cells (Tregs). Furthermore, ATO represents a reasonable salvage treatment in some patients with refractory severe aplastic anemia (SAA). The current study aimed to evaluate the function of ATO on the Tregs percentage and cytokines changes in the peripheral blood mononuclear cells (PBMCs) of SAA patients. PBMCs were collected from 20 newly diagnosed SAA patients in Henan Cancer Hospital and treated with different concentrations of ATO (0, 1, 2.5, and 5 μmol/L). Then we investigated the efficacy of ATO on Tregs ratio and the levels of interferon (IFN)-γ, interleukin (IL)-4, IL-17 and transforming growth factor (TGF)-β1 in the peripheral blood of SAA patients in vitro. The results showed that ATO significantly increased the proportion of Tregs ( P < .001) at 2.5 and 5 μmol/L concentrations, and the proportion of Tregs was increased with increasing ATO concentration (r = 0.524). At 1 ( P = .03), 2.5 ( P < .001) and 5 μmol/L ( P < .001), ATO significantly up-regulated the expression levels of Foxp3 mRNA, which was positively and linearly correlated with the increase of Tregs cell-frequency ( r = 0.52, 95%CI, 0.37–0.67). In addition, ATO significantly reduced the levels of IFN-γ (at 1, 2.5 and 5 μmol/L, P < .001), IL-4 (at 2.5 μmol/L, P = .009; at 5 μmol/L, P < .001), and IL-17 (at 2.5, P = .016; at 5 μmol/L, P < .001). ATO significantly reduced the levels of TGF-β1 at 5 μmol/L ( P = .03), but showed no significant effects at 1 and 2.5 μmol/L ( P > .05). ATO could mediate the immune regulation, which might contribute to improve hematopoietic recovery in SAA patients.