The advantage of Sirolimus in amplifying regulatory B cells and regulatory T cells in liver transplant patients.
Eur J Pharmacol
; 869: 172872, 2020 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-31846626
ABSTRACT
Sirolimus has been shown to ameliorate steroid-resistant rejection and induce long-term immune tolerance among liver transplant patients. However, the detailed mechanism of how Sirolimus achieve these advantages is still lacking. This study attempts to reveal some possible mechanisms by investigating regulatory B cells (Bregs), regulatory T cells (Tregs) and some cytokines in liver transplant recipients whose Tacrolimus was partially converted to Sirolimus. The results showed that CD19+CD24+CD38+Bregs and CD4+CD25+FoxP3+Tregs increased significantly during the first month after drug conversion (P < 0.01 and P < 0.05). The percentages of IL-10+Bregs and TGF-ß1+Bregs were also elevated (P < 0.05 and P < 0.01), and the same trend was observed in the levels of IL-10 and TGF-ß1 (P < 0.01 and P < 0.01). However, in the observation period, these investigated lymphocyte subsets and cytokines didn't change significantly in patients without Sirolimus usage. The incidence of biliary stenosis in the conversion group were significantly lower than that in the control group (P < 0.05). At the same time, in vitro experiments showed that Sirolimus could significantly amplify Bregs and Tregs (P < 0.01 and P < 0.01) while Tacrolimus did not show the amplifications effects. Sirolimus' function of amplifying Bregs was weakened, and its function of amplifying Tregs even disappeared after IL-10 and TGF-ß1 were neutralized. In conclusion, Sirolimus could amplify Bregs and Tregs among liver transplant recipient, which might be benefit to mitigate the immune response, decrease chances of rejection and alleviate biliary complication. IL-10 and TGF-ß1 may play important roles during this process.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transplante de Fígado
/
Tacrolimo
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Linfócitos T Reguladores
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Sirolimo
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Linfócitos B Reguladores
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Imunossupressores
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Eur J Pharmacol
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China