Cytokine--chemokine and apoptotic signatures in patients with hepatitis C

Transl Res. 2007 Mar;149(3):126-36. doi: 10.1016/j.trsl.2006.11.002.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Biomarkers / blood
  • Biopsy
  • Chemokine CCL2 / blood
  • Chemokine CCL5 / blood
  • Chemokines / blood*
  • Cytokines / blood*
  • Fibrosis
  • Hepatitis C, Chronic / blood
  • Hepatitis C, Chronic / immunology*
  • Hepatitis C, Chronic / pathology*
  • Hepatocytes / immunology
  • Hepatocytes / pathology
  • Hepatocytes / ultrastructure
  • Humans
  • Interleukin-12 / blood
  • Interleukin-18 / blood
  • Interleukin-2 / blood
  • Interleukin-6 / blood
  • Liver / immunology
  • Liver / metabolism
  • Liver / pathology
  • Microscopy, Electron
  • Nuclear Proteins / blood
  • Severity of Illness Index
  • Transforming Growth Factor beta / blood
  • Tumor Necrosis Factor-alpha / metabolism
  • fas Receptor

Substances

  • Biomarkers
  • CCL2 protein, human
  • Chemokine CCL2
  • Chemokine CCL5
  • Chemokines
  • Cytokines
  • Interleukin-18
  • Interleukin-2
  • Interleukin-6
  • NAP1L4 protein, human
  • Nuclear Proteins
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • fas Receptor
  • Interleukin-12