title: Progressive liver injury in chronic hepatitis C infection is related to altered cellular immune response and to different citokine profile.
abstract: Natural immune responses, both cellular and humoral, are not capable of terminating HCV infection in most patients. The aim of this study was to evaluate: a) the importance of the immune system in the pathogenesis of chronic HCV infection; b) analysis of successful immunoresponses in persons infected with C virus; c) immuno mechanisms in the progression of hepatic damage; d) different cytokine profiles from patients with persistent and self-limited hepatitis C virus infection; e) development of new antiviral strategies when virus is resistant to interferon treatment. The inadequate T helper1 (Th1) immunity as well as the weak HCV-specific T-cell response at the site of inflammation is associated with failure to clear the virus and a chronic course of disease. The production of interleukin 12 (IL-12) is critical for induction of Th1 immunity, directed towards elimination of intracellular pathogenes and viruses. The core protein of HCV seems to have a suppressive action on IL-12 production at the transcriptional level. The specific Th1 cell defect is correlated with insufficient Th and CTL responses, and lower production of type 1 cytokine (IL-2, IFN-gamma, lymphokine-activated killer cells). Taken together, these results are probably responsible for non-eradication of HCV infection. Particularly the effects of interferon-gamma may include inhibition of HCV virion production by an effect on viral RNA and protein synthesis, enhancement of immune lysis of HCV infected cells, inhibition of hepatic fibrosis by an effect on TGF-beta, and an effect on HCV induced carcinogenesis. These data suggest an HCV-related cellular immune defect in patients with hepatitis C that can be restored in most patients by IL-12. New approaches using a combination of nucleoside analogs or other strategies, such as immune intervention (DNA vaccine, stimulation of the Th1 response) or gene therapy (antisense oligonucleotides dominant negative mutants) should therefore be evaluated in animal models to optimize the current antiviral protocols.
authors.affiliation: F. Magrassi Department of Clinical and Experimental Medicine, II University of Naples School of Medicine, Naples, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Cecere
authors.forename: F
authors.initials: F
authors.lastname: Marotta
authors.forename: B
authors.initials: B
authors.lastname: Vangieri
authors.forename: L
authors.initials: L
authors.lastname: Tancredi
authors.forename: A
authors.initials: A
authors.lastname: Gattoni
mesh_terms: D000917:Antibody Formation; D016207:Cytokines / Q000097:blood*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D008099:Liver / Q000276:immunology* / Q000473:pathology*
chemical_list: D016207:Cytokines