Effects of oxymatrine on the serum levels of T helper cell 1 and 2 cytokines and the expression of the S gene in hepatitis B virus S gene transgenic mice: a study on the anti-hepatitis B virus mechanism of oxymatrine.

Background: Oxymatrine has been shown to have a remarkable inhibitory activity to hepatitis B virus (HBV) infection with a hepatitis B virus e antigen (HBeAg) serum conversion rate of approximately 45%. In order to explore the anti-HBV mechanism of oxymatrine, the effects of oxymatrine on serum levels of T helper (h) 1 cytokines (interferon (IFN)-y and interleukin (IL)-2) and Th2 cytokines (IL-4 and IL-10), and the expression of S gene in HBV S gene transgenic mice were studied. Methods: Each transgenic mouse was either injected with oxymatrine or saline intraperitoneally once a day for 30 days. Serum levels of IFN-y, IL-2, IL-4 and IL-10 were quantitated and compared to the data before the treatment. The expression of HBV S gene in transgenic mice was analyzed at the DNA, mRNA and protein levels. Results: The serum levels of IFN-y in transgenic mice before or after oxymatrine treatment were 3.108±3.172 and 11.059±6.971 pg/mL, respectively. In contrast, serum levels before and after oxymatrine treatment for IL-4 were 29.045±13.235 and 13.024±9.002 pg/mL. respectively (P<0.001). The serum levels of IL-2 in the control (saline injection) and oxymatrine-treated mice were 1.070±0.447 and 5.537±2.887 pg/mL, respectively (P<0.0001); and that of IL-10 were 97.226±73.306 and 33.607±23.154pg/mL, respectively (P<0.01). No significant differences were observed in the expression of HBV S gene in the transgenic mice at the DNA, mRNA and protein levels before or after oxymatrine treatment. Conclusions: The fact thatThl cytokines are increased while Th2 cytokines are decreased suggests that oxymatrine treatment triggers the change of immune response to hepatitis B infection in transgenic mice, which leads to improved HBV inhibitory activities. The study can help us better understand the mechanisms of the anti-HBV drug, oxymatrine, and how it has potential as an application in clinical chronic hepatitis B treatment.