Expression rate of cytokine mRNA in the liver of chronic hepatitis C: comparison with chronic hepatitis B.
This study was carried out to test the hypothesis that, in chronic hepatitis (CH), inflammatory processes, including viral replication, host immune response, and hepatocyte destruction, are regulated by a cytokine network in the liver. Expression of the mRNA of the cytokines IL1-beta, IL2, IL4, IL5, IL6, TNF-alpha, and IFN-gamma, the lymphocyte markers CD4 and CD8, and the HLA class I molecule, beta 2-microglobulin (B2MG) in the liver tissue of 20 CH(C) cases and 9 CH(B) patients was investigated by the reverse transcription polymerase chain reaction (RT-PCR) method. TNF-alpha, CD4, and B2MG mRNA were detected in 100% of cases of in both CH(B) and CH(C). The expression rates of IL1-beta, IL2, IL4, IFN-gamma, and CD8 mRNA were 80%, 40%, 25%, 40%, and 80% in CH(C) and 88.9%, 44.5%, 30%, 55.6%, and 100% in CH(B). IL6 mRNA was detected only in CH(B), in 22.2% of cases, IL5 mRNA was not detected in either CH(B) or CH(C). IL2, IL4, and IFN-gamma mRNA were expressed significantly more frequently in patients who had high serum ALT and a high histological activity index (HAI) score. There was no difference in cytokine expression between CH(B) and CH(C), except in IL6, suggesting the existence of a common immunopathogenesis for CH(B) and CH(C). In chronic viral hepatitis, IL1-beta and TNF-alpha appear to play a major role in immune responses and IL2, IL4, and IFN-gamma seem to be associated with increased cytotoxic T cell response.(ABSTRACT TRUNCATED AT 250 WORDS)
Fukuda
R
R
Second Department of Internal Medicine, Shimane Medical University, Japan.
Satoh
S
S
Nguyen
X T
XT
Uchida
Y
Y
Kohge
N
N
Akagi
S
S
Ikeda
S
S
Watanabe
M
M
Fukumoto
S
S
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D015703:Antigens, CD / Q000235:genetics; D001483:Base Sequence; D016009:Chi-Square Distribution; D002908:Chronic Disease; D016207:Cytokines / Q000235:genetics*; D005260:Female; D006509:Hepatitis B / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006526:Hepatitis C / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008099:Liver / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D015703:Antigens, CD; D016207:Cytokines; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma; D000410:Alanine Transaminase