The presence of high amounts of HBV-DNA in serum is associated with suppressed costimulatory effects of interleukin 12 on HBV-induced immune response

Background/Aims: The aim of this study was to examine the influence of the viral load on costimulatory effects of rhIL-I2 on the hepatitis B virus (HB V)-induced immune response. Methods: Peripheral blood mononuclear cells of HBsAg positive patients with out cirrhosis were stimulated with HBsAg, HBcAg, preS1Ag and tetanus toxoid in the absence or presence of IL-12 (0.01, 0.1 and 1 ng/ml). Stimulation b y alpha-CD3+alpha-CD28, pokeweed mitogen (PWM) and lipopolysaccharide (LPS) were used as controls. Then, proliferation and cytokine production were de termined by H-3-thymidine uptake and ELISA after 72 h. The patients were di vided into group 1 (n=21): HBV-DNA: not detectable, group 2 (n=13): HBV-DNA : <300 pg/ml, and group 3 (n 10): HBV-DNA: >300 pg/ml. Results: After stimulation with only HBV antigens, the highest amounts of I L-10 were found in group 3, while interferon (IFN)-gamma was rarely detecta ble. After stimulation with IL-12 and HBV antigens, strong costimulatory ef fects on IFN-gamma production, as well as proliferation, were observed in a ll patients except individuals from group 3. With regard to antigen-unrelat ed stimulation, significantly lower amounts of LPS-induced IFN-gamma produc tion and alpha-CD3+28 induced proliferative responses, but higher amounts o f LPS-induced IL-10 were observed in group 3. Conclusions: These data suggest that the presence of high amounts of HBV-DN A in serum is associated with suppressed co-stimulatory and regulatory effe cts of IL-12 on the immune response to HBV antigens. This may be one explan ation for the poor response to immunostimulating therapy in patients with a high viral load.