HBV‐specific immune defect in chronic hepatitis B (CHB) is correlated with a dysregulation of pro‐ and anti‐inflammatory cytokines

The aim of this study was to examine the immunomodulating effects of rhIL-12 on the immune response induced by hepatitis B virus (HBV) antigens in clinical subgroups of patients with HBV infection. Peripheral blood mononuclear cells (PBMC) of 80 patients 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 anti-CD3 + anti-CD28 and lipopolysaccharide (LPS) were used as controls. Proliferation and cytokine production were determined by 3 H-thymidine uptake and ELISA after 72 h. After stimulation with HBV antigens only, production of tumour necrosis factor-alpha (TNF-α) or IL-10 was observed in all patients, while interferon-gamma (IFN-γ) was detectable in only 27 patients. After costimulation with IL-12 and HBV antigens, however, large amounts of IFN-γ were found in all patients, while HBV-induced IL- 10 production remained mostly unchanged. When clinical subgroups including patients with compensated liver cirrhosis were compared, PBMC from patients with HBeAg + hepatitis showed the lowest capacity to produce IFN-γ after HBV antigen-positive IL-12. These data suggest that the ability of IL-12 to enhance IFN-γ production against HBV antigens is correlated with the presence of HBeAg and is not impaired in patients with advanced liver disease. In addition, IL-12 and IL-10 production by antigen-presenting cells may be a critical factor that determines the efficacy of the immune response against the hepatitis B virus.