title: Cytokine--chemokine and apoptotic signatures in patients with hepatitis C.
abstract: Cytokines and chemokines are proteins that play a critical role in the regulation of immunity and inflammation in patients with chronic Hepatitis C. The aim of our study was to correlate serum cytokines, chemokines and apoptosis in non-treated chronic hepatitis C patients with various degrees of inflammation and fibrosis. We studied 778 patients: 59 had low Knodell fibrosis score and low Knodell histological activity index; 372 had mild fibrosis and low histological activity index; 270 had moderate fibrosis and moderate histological activity index; and, 77 had high fibrosis and high histological activity index on their biopsy. Serum cytokines, chemokines and apoptosis were measured by enzyme-linked-immunosorbent-assay. Multivariate analysis was employed for statistical purposes. A positive correlation was seen between the degree of inflammation and tumor necrosis factor-alpha (TNF-alpha) levels (r = 0.92) in non-cirrhotic patients and between interleukin 2 in all patients (r = 0.85). Interleukin-8 increased significantly at higher histological activity indices and continued to increase in patients with cirrhosis. Transforming growth factor-beta (TGF-beta) levels increased significantly with the severity of fibrosis, but decreased in cirrhotics. In conclusion, cytokines, chemokines and apoptosis levels reflect the progression of inflammation and fibrosis in hepatitis C infected patients, but their signatures differ.
authors.affiliation: In Vitro Drug Safety and Biotechnology, MaRS Discovery Center, 101 College Street, Lab 351, Toronto, Ontario, M5G 1L7 Canada. manuela@sten.sunnybrook.utoronto.ca
authors.forename: Manuela G
authors.initials: MG
authors.lastname: Neuman
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Benhamou
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
authors.forename: Dominique
authors.initials: D
authors.lastname: Valla
authors.forename: Izabella M
authors.initials: IM
authors.lastname: Malkiewicz
authors.forename: Gad G
authors.initials: GG
authors.lastname: Katz
authors.forename: Cristhian
authors.initials: C
authors.lastname: Trepo
authors.forename: Marc
authors.initials: M
authors.lastname: Bourliere
authors.forename: Ross G
authors.initials: RG
authors.lastname: Cameron
authors.forename: Lawrence
authors.initials: L
authors.lastname: Cohen
authors.forename: Mary
authors.initials: M
authors.lastname: Morgan
authors.forename: Hemda
authors.initials: H
authors.lastname: Schmilovitz-Weiss
authors.forename: Ziv
authors.initials: Z
authors.lastname: Ben-Ari
mesh_terms: D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D018932:Chemokine CCL2 / Q000097:blood; D018946:Chemokine CCL5 / Q000097:blood; D018925:Chemokines / Q000097:blood*; D016207:Cytokines / Q000097:blood*; D005355:Fibrosis; D019698:Hepatitis C, Chronic / Q000097:blood / Q000276:immunology* / Q000473:pathology*; D022781:Hepatocytes / Q000276:immunology / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D018664:Interleukin-12 / Q000097:blood; D020382:Interleukin-18 / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008854:Microscopy, Electron; D009687:Nuclear Proteins / Q000097:blood; D012720:Severity of Illness Index; D016212:Transforming Growth Factor beta / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019014:fas Receptor
chemical_list: D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D018925:Chemokines; D016207:Cytokines; D020382:Interleukin-18; D007376:Interleukin-2; D015850:Interleukin-6; C104356:NAP1L4 protein, human; D009687:Nuclear Proteins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D018664:Interleukin-12