The presence of high amounts of HBV-DNA in serum is associated with suppressed costimulatory effects of interleukin 12 on HBV-induced immune response.
OBJECTIVE
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, preS1Ag and tetanus toxoid in the absence or presence of IL-12 (0.01, 0.1 and 1 ng/ml). Stimulation by alpha-CD3+alpha-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)-gamma was rarely detectable. After stimulation with IL-12 and HBV antigens, strong costimulatory effects on IFN-gamma 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-gamma production and alpha-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.
Schlaak
J F
JF
First Department of Medicine, University of Mainz, Germany. schlaak@mail.uni-mainz.de
Tully
G
G
Löhr
H F
HF
Gerken
G
G
Meyer zum Büschenfelde
K H
KH
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D004279:DNA, Viral / Q000097:blood*; D006509:Hepatitis B / Q000097:blood / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D018664:Interleukin-12 / Q000276:immunology* / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology
D000276:Adjuvants, Immunologic; D004279:DNA, Viral; D018664:Interleukin-12