Evidence for a sub-morphological inflammatory process in the liver in haemochromatosis

J Hepatol. 2003 Apr;38(4):426-33. doi: 10.1016/s0168-8278(02)00444-0.

Abstract

Background/aims: The role of cytokines in hepatic injury has been examined for many liver diseases however little is known of the cytokine involvement in haemochromatosis. The aim of the current study was to examine the hepatic gene expression of potential proinflammatory and profibrogenic cytokines in haemochromatosis.

Methods: Interferon-gamma, interleukin-10, transforming growth factor-beta(1) and tumor necrosis factor-alpha mRNA expression was assessed in liver tissue from 20 haemochromatosis patients, eight controls and eight chronic hepatitis C patients. To assess the immunophenotype of the inflammatory infiltrate in haemochromatosis, liver sections were subjected to immunohistochemistry using markers for macrophages (CD68, HAM56, MAC387) or T cells (CD3 and CD45RO).

Results: Interferon-gamma mRNA was increased in both haemochromatosis (0.29+/-0.08%, P=0.01) and hepatitis C patients (1.02+/-0.32%, P=0.03) compared to controls (0.04+/-0.01%). Interleukin-10 mRNA was significantly decreased in both haemochromatosis and hepatitis C patients (0.01+/-0.003%, P=0.008 and 0.03+/-0.015%, P=0.02, respectively) compared to controls (0.12+/-0.01%). CD3 positive T-cell number was significantly correlated with increasing hepatic iron concentration (r=0.56, P=0.03).

Conclusions: This study has demonstrated a distinct pattern of cytokine gene expression in haemochromatosis, which resembles that of inflammatory conditions such as chronic hepatitis C. These factors may play a role in the development of iron-induced hepatic fibrosis in haemochromatosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Comment

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Antigens, CD / analysis
  • Antigens, Differentiation, Myelomonocytic / analysis
  • Biomarkers
  • CD3 Complex / analysis
  • Gene Expression / immunology
  • Hemochromatosis / immunology*
  • Hemochromatosis / pathology*
  • Hepatitis C / immunology
  • Hepatitis C / pathology
  • Humans
  • Immunohistochemistry
  • Interferon-gamma / genetics
  • Interleukin-10 / genetics
  • Iron / analysis
  • Leukocyte Common Antigens / analysis
  • Liver / chemistry
  • Liver / immunology*
  • Liver / pathology*
  • Liver Cirrhosis / immunology
  • Liver Cirrhosis / pathology
  • RNA, Messenger / analysis
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Biomarkers
  • CD3 Complex
  • CD68 antigen, human
  • HAM-56 antibody
  • RNA, Messenger
  • TGFB1 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interferon-gamma
  • Iron
  • Leukocyte Common Antigens