title: Modulation of the anti-inflammatory interleukin 10 and of proapoptotic IL-18 in patients with chronic hepatitis C treated with interferon alpha and ribavirin.
abstract: The aim of this work was to analyse apoptosis rate, measured by the serum levels of proapoptotic interleukin (IL)-18 and of soluble Fas (sFas), as well as of anti-inflammatory IL-10, in patients with chronic hepatitis C, at baseline and after treatment with interferon alpha and ribavirin. Twenty-seven patients with biopsy-proven chronic hepatitis C were studied, at baseline and after treatment with interferon alpha (21 cases) or pegylated interferon (6 cases) plus ribavirin. A group of 15 healthy sex- and age-matched individuals was selected as control. Serum concentrations of sFas, IL-10 and IL-18 were determined by ELISA in sandwich. The relationship of these molecules to necro-inflammatory and fibrotic activity was evaluated. Evolution of the serum concentrations of these molecules was analysed after treatment. Significantly increased serum concentrations of sFas were detected in patients with chronic hepatitis, compared with controls. Levels of this molecule were significantly correlated with necroinflammatory activity. Likewise, concentrations of IL-10 were significantly increased in the group of patients, compared with controls. Treatment with interferon and ribavirin induced a significant decrease of IL-18 concentration independently of the viral response. In contrast, levels of sFas decreased only in those patients with sustained response to therapy. Finally, baseline levels of IL-10 were significantly increased in patients without response to treatment, compared with those with sustained response, but the concentration did not change with the treatment. Increased serum levels of IL-10 are a negative prognostic marker of response to hepatitis C treatment. A significant decrease of apoptotic rate, as determined by sFas, can be expected in patients with a response to therapy.
authors.affiliation: Servicios de Aparato Digestivo, Hospital Universitario Puerta del Mar, Cádiz, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Marín-Serrano
authors.forename: C
authors.initials: C
authors.lastname: Rodríguez-Ramos
authors.forename: F
authors.initials: F
authors.lastname: Díaz
authors.forename: L
authors.initials: L
authors.lastname: Martín-Herrera
authors.forename: J A
authors.initials: JA
authors.lastname: Girón-González
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D016022:Case-Control Studies; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000097:blood*; D020382:Interleukin-18 / Q000097:blood*; D008297:Male; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011446:Prospective Studies; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D018709:Statistics, Nonparametric; D019014:fas Receptor / Q000097:blood
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D020382:Interleukin-18; D011994:Recombinant Proteins; D019014:fas Receptor; D016753:Interleukin-10; D011092:Polyethylene Glycols; D012254:Ribavirin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C100416:peginterferon alfa-2a