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Effect 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.
Medicine (Baltimore). 2020 Jun 26; 99(26):e20630.M

Abstract

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.

Authors+Show Affiliations

Henan Key Lab of Experimental Haematology, Henan Center of Excellence in Tissue Engineering, Department of Hematology, Henan Cancer Hospital, Henan Cancer Hospital affiliated to Zhengzhou University, Zhengzhou University, Zhengzhou, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32590737

Citation

Zhao, Juanjuan, et al. "Effect 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." Medicine, vol. 99, no. 26, 2020, pp. e20630.
Zhao J, Song Y, Liu L, et al. Effect 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. Medicine (Baltimore). 2020;99(26):e20630.
Zhao, J., Song, Y., Liu, L., Yang, S., & Fang, B. (2020). Effect 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. Medicine, 99(26), e20630. https://doi.org/10.1097/MD.0000000000020630
Zhao J, et al. Effect 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. Medicine (Baltimore). 2020 Jun 26;99(26):e20630. PubMed PMID: 32590737.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect 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. AU - Zhao,Juanjuan, AU - Song,Yongping, AU - Liu,Lina, AU - Yang,Shiwei, AU - Fang,Baijun, PY - 2020/6/27/entrez PY - 2020/6/27/pubmed PY - 2020/7/8/medline SP - e20630 EP - e20630 JF - Medicine JO - Medicine (Baltimore) VL - 99 IS - 26 N2 - 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. SN - 1536-5964 UR - https://www.unboundmedicine.com/medline/citation/32590737/Effect_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 L2 - https://doi.org/10.1097/MD.0000000000020630 DB - PRIME DP - Unbound Medicine ER -