Evidence for a sub-morphological inflammatory process in the liver in haemochromatosis.
OBJECTIVE
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.
Bridle
Kim R
KR
Hepatic Fibrosis Group, Population Health and Clinical Sciences Division, The Queensland Institute of Medical Research, Post Office, Royal Brisbane Hospital, Herston, Qld 4029, Australia.
Crawford
Darrell H G
DH
Fletcher
Linda M
LM
Smith
Jeffery L
JL
Powell
Lawrie W
LW
Ramm
Grant A
GA
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D015415:Biomarkers; D017252:CD3 Complex / Q000032:analysis; D015870:Gene Expression / Q000276:immunology; D006432:Hemochromatosis / Q000276:immunology* / Q000473:pathology*; D006526:Hepatitis C / Q000276:immunology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D007501:Iron / Q000032:analysis; D017493:Leukocyte Common Antigens / Q000032:analysis; D008099:Liver / Q000737:chemistry / Q000276:immunology* / Q000473:pathology*; D008103:Liver Cirrhosis / Q000276:immunology / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D000097382:CD68 Molecule
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D017252:CD3 Complex; D007371:Interferon-gamma; D016753:Interleukin-10; D007501:Iron; D017493:Leukocyte Common Antigens; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C096893:HAM-56 antibody; C508960:TGFB1 protein, human