摘要
Suppressor of cytokine signaling （SOCS） 1 plays a crucial role in the immune response and might contribute to the prognoses of liver failure treated with glucocorticoid. We recruited 47 acute-on-chronic hepatitis B liver failure （ACHBLF） patients receiving glucocorticoid treatment and 30 healthy controls to determine the potential effects of glucocorticoid on the transcriptional level of SOCS1 in peripheral blood mononuclear cells. On the third and twenty-eighth days of glucocorticoid treatment, SOCS1 expression was negatively correlated with model for end-stage liver disease （MELD） score. Interleukin-6 （IL-6） and tumor-necrosis factor-a （＇I＇NF-a） levels were statistically lower, while the SOCS1 transcription level was higher in survivors than non-survivors both in pre- and post-treatment ACHBLF patients. The methylation rate of the SOCS1 promoter in ACHBLF patients was higher than in healthy control patients as determined by methylation-specific polymerase chain reaction. The mRNA level of SOCS1 in methylated promoters was significantly lower than from patients with unmethylated SOCS1 promoters, interferon （IFN）-y-responsive and STATl-dependent gene expression was higher in survivors and was dramatically decreased with rising expression of SOCS1 after glucocorticoid treatment. Mortality rates were significantly higher in methylated patients than for those without methylation at the end of a 90-day follow-up. Furthermore, we found that five in six surviving patients displayed demethylated SOCS1 on the twenty-eighth day after treatment, while that number was 3 in 10 in the non-survivors. These findings suggested that ACHBLF patients without SOCS1 methylation may have a favorable response to corticosteroid treatment.
Suppressor of cytokine signaling （SOCS） 1 plays a crucial role in the immune response and might contribute to the prognoses of liver failure treated with glucocorticoid. We recruited 47 acute-on-chronic hepatitis B liver failure （ACHBLF） patients receiving glucocorticoid treatment and 30 healthy controls to determine the potential effects of glucocorticoid on the transcriptional level of SOCS1 in peripheral blood mononuclear cells. On the third and twenty-eighth days of glucocorticoid treatment, SOCS1 expression was negatively correlated with model for end-stage liver disease （MELD） score. Interleukin-6 （IL-6） and tumor-necrosis factor-a （＇I＇NF-a） levels were statistically lower, while the SOCS1 transcription level was higher in survivors than non-survivors both in pre- and post-treatment ACHBLF patients. The methylation rate of the SOCS1 promoter in ACHBLF patients was higher than in healthy control patients as determined by methylation-specific polymerase chain reaction. The mRNA level of SOCS1 in methylated promoters was significantly lower than from patients with unmethylated SOCS1 promoters, interferon （IFN）-y-responsive and STATl-dependent gene expression was higher in survivors and was dramatically decreased with rising expression of SOCS1 after glucocorticoid treatment. Mortality rates were significantly higher in methylated patients than for those without methylation at the end of a 90-day follow-up. Furthermore, we found that five in six surviving patients displayed demethylated SOCS1 on the twenty-eighth day after treatment, while that number was 3 in 10 in the non-survivors. These findings suggested that ACHBLF patients without SOCS1 methylation may have a favorable response to corticosteroid treatment.
基金
ACKNOWLEDGEMENTS This work was supported by grants from the Key Project of Chinese Ministry of Science and Technology （2012ZX10002007, 2013ZX 10002001） and National Natural Science Foundation of China （81171579, 81201287）.
