title: Endogenous levels of mRNA for IFNs and IFN-related genes in hepatic biopsies of chronic HCV-infected and non-alcoholic steatohepatitis patients.
abstract: To investigate the intra-hepatic activation of the IFN system in patients affected by chronic HCV-infection in comparison with that observed in a non-infectious liver disease such as non-alcoholic steatohepatitis, we measured the liver steady state mRNA levels of interferon-alpha, interferon-beta and interferon-gamma as well as of IFN-related genes (IFNAR-1, STAT1alpha, PKR, 2-5 AS, IRF-1, ICE and IL-18). In HCV-infected subjects, possible correlations of these parameters with viral load and liver injury were also analyzed. Twenty-four chronic untreated HCV-infected subjects and seven patients with non-alcoholic steatohepatitis were enrolled in the study. Liver biopsies were graded according to Knodell scores. Intra-hepatic mRNA levels of IFNs and related genes were assessed by semi-quantitative RT-PCR. In comparison with non-alcoholic steatohepatitis, in HCV-infected subjects IFN-alpha and -beta mRNA levels were significantly lower, whereas IFN-gamma, IFNAR-1, STAT1alpha IRF-1, and IL-18 mRNA were upregulated. Moreover, IFN-gamma mRNA steady state levels were correlated positively with those of IFNAR-1, IRF-1, and IL-18, suggesting a coordinated induction of these genes. Although plasma viral load was correlated inversely with IL-18-specific mRNA, viral load was not related to liver injury. IFN-gamma and IRF-1 mRNA levels were correlated positively with ALT, but not with the grading or staging. Conversely, IFN-alpha and -beta mRNA levels were higher in livers with lower staging scores. These findings support the hypothesis that in chronic HCV infection there is an imbalance between an upregulated IFN-gamma system and a downregulated IFN-alpha and -beta system, probably due to a mixed effect exerted by HCV-specific and inflammatory non-specific factors.
authors.affiliation: Microbiology and Virology Service, S. Pertini Hospital, Rome, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Abbate
authors.forename: Mario
authors.initials: M
authors.lastname: Romano
authors.forename: Roberta
authors.initials: R
authors.lastname: Longo
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Cappiello
authors.forename: Oreste
authors.initials: O
authors.lastname: Lo Iacono
authors.forename: Vito
authors.initials: V
authors.lastname: Di Marco
authors.forename: Concetta
authors.initials: C
authors.lastname: Paparella
authors.forename: Alberto
authors.initials: A
authors.lastname: Spano
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Capobianchi
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D016174:Hepacivirus / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000473:pathology / Q000821:virology; D006801:Humans; D050856:Interferon Regulatory Factor-1; D007372:Interferons / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000276:immunology* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000235:genetics / Q000378:metabolism; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
chemical_list: D004268:DNA-Binding Proteins; C507964:IFNAR1 protein, human; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D020382:Interleukin-18; D008565:Membrane Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D017471:Receptors, Interferon; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D053633:Receptor, Interferon alpha-beta; D007372:Interferons