| ObjectiveThe effect of the basal 2', 5'-Oligoadenylate synthetase(2-5 AS) activity in peripheral blood mononuclear cells of the patients with chronic hepatitis B on the changes of interferon alpha(IFNa) signaling molecules was investigated. The purpose of this work was to study the mechanism of IFNa therapy efficacy in patients with chronic hepatitis B. The study was expected to help select suitable patients for IFNa therapy and prepare new antiviral drugs on IFNa signal transduction level.MethodsPeripheral blood mononuclear cells of 45 patients with chronic hepatitis B were investigated. Of the total peripheral blood mononuclear cell samples obtained, some were used for determination of basal 2-5 AS activity. The remaining cells were divided into two groups and cultured for 24 h in either the absence (basal group in vitro) or presence (induced group in vitro) of 1000 lU/ml of IFNa. The activity of 2-5 AS, the expression of IFNa receptor (IFNaR) and the levels of Jakl, Stall and Stat2 in PBMC were detected. The relationships between basal 2-5AS activity and the changes of 2-5AS, IFNaR, Jakl, Statl and Stat2 (the ratios of induced/basal level in vitro) were evaluated.ResultsAfter a 24 h culture of PBMC in IFNa, 2-5AS, Jakl, Statl and Stat2 increased significantly (P<0.05). However the expression of IFNaR decreased simultaneously (P<0.05). There were inverse correlations between basal 2-5AS activity and the changes of 2-5AS and Statl (P<0.05). No correlations were found between basal 2-5AS activity and the changes of IFNaR, Jakl and Stat2 (P>0.05).ConclusionsBasal 2-5AS activity may downregulate the sensitivity of PBMC to exogenous IFNa. Decreased induction of Statl may be responsible for the mechanism of the downregulation. High level of basal 2-5AS activity may be one of the mechanisms of poor efficacy of IFNa therapy in patients with chronic hepatitis B.
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