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

The aim of this study was to examine the immunomodulating effects of rhIL-1 2 on the immune response induced by hepatitis B virus (HBV) antigens in cli nical subgroups of patients with HBV infection. Peripheral blood mononuclea r cells (PBMC) of 80 patients were stimulated with HBsAg, HBcAg, pre-S1Ag a nd tetanus toxoid in the absence or presence of IL-12 (0.01, 0.1 and 1 ng/m l). Stimulation by anti-CD3 + anti-CD28 and lipopolysaccharide (LPS) were u sed as controls. Proliferation and cytokine production were determined by H -3-thymidine uptake and ELISA after 72 h. After stimulation with HBV antige ns only, production of tumour necrosis factor-alpha (TNF-alpha) or IL-10 wa s observed in all patients, while interferon-gamma (IFN-gamma) was detectab le in only 27 patients. After costimulation with IL-12 and HBV antigens, ho wever, large amounts of IFN-gamma were found in all patients, while HBV-ind uced IL-10 production remained mostly unchanged. When clinical subgroups in cluding patients with compensated liver cirrhosis were compared, PBMC from patients with HBeAg+ hepatitis showed the lowest capacity to produce IFN-ga mma after HBV antigen-positive IL-12. These data suggest that the ability o f IL-12 to enhance IFN-gamma production against HBV antigens is correlated with the presence of HBeAg and is not impaired in patients with advanced li ver 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 r esponse against the hepatitis B virus.