title: HBV-specific immune defect in chronic hepatitis B (CHB) is correlated with a dysregulation of pro- and anti-inflammatory cytokines.
abstract: 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, pre-S1Ag 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 3H-thymidine uptake and ELISA after 72 h. After stimulation with HBV antigens only, production of tumour necrosis factor-alpha (TNF-alpha) or IL-10 was observed in all patients, while interferon-gamma (IFN-gamma) was detectable in only 27 patients. After costimulation with IL-12 and HBV antigens, however, large amounts of IFN-gamma 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-gamma after HBV antigen-positive IL-12. These data suggest that the ability of 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 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.
authors: First Department of Medicine, University of Mainz, Germany. schlaak@mail.uni-mainz.de
authors: J F
authors: JF
authors: Schlaak
authors: G
authors: G
authors: Tully
authors: H F
authors: HF
authors: Löhr
authors: G
authors: G
authors: Gerken
authors: K H
authors: KH
authors: Meyer zum Büschenfelde
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis*; D004279:DNA, Viral / Q000097:blood; D006510:Hepatitis B Antibodies / Q000097:blood; D006511:Hepatitis B Antigens / Q000008:administration & dosage / Q000097:blood; D006515:Hepatitis B virus / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000145:classification / Q000276:immunology* / Q000821:virology; D006801:Humans; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006511:Hepatitis B Antigens; D018836:Inflammation Mediators; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma