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-12 on the hepatitis B virus (HBV)-induced immune response. Methods: Peripheral blood mononuclear cells of HBsAg positive patients without cirrhosis were stimulated with HBsAg, HBcAg, preSlAg and tetanus toxoid in the absence or presence of IL-12 (0.01, 0.1 and 1 ng/ml). Stimulation by α-CD3+α-CD28, pokeweed mitogen (PWM) and lipopolysaccharide (LPS) were used as controls. Then, proliferation and cytokine production were determined by 3H-thymidine uptake and ELISA after 72 h. The patients were divided 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 IL-10 were found in group 3, while interferon (IFN)-γ was rarely detectable. After stimulation with IL-12 and HBV antigens, strong costimulatory effects on IFN-γ production, as well as proliferation, were observed in all patients except individuals from group 3. With regard to antigen-unrelated stimulation, significantly lower amounts of LPS-induced IFN-γ production and α-CD3+28 induced proliferative responses, but higher amounts of LPS-induced IL-10 were observed in group 3. Conclusions: These data suggest that the presence of high amounts of HBV-DNA in serum is associated with suppressed co-stimulatory and regulatory effects of IL-12 on the immune response to HBV antigens. This may be one explanation for the poor response to immunostimulating therapy in patients with a high viral load.