Modulation of tumor necrosis factor receptors 1 and 2 in chronic hepatitis B and C: the differences and implications in pathogenesis.
Tumor necrosis factor (TNF) plays a role in the pathogenesis of chronic hepatitis B (CHB) and chronic hepatitis C (CHC). The difference in the cytokine responses between hepatitis B virus (HBV) and hepatitis C virus (HCV) infections may have implications in the pathogenesis of these diseases. We performed a comparative study to examine the possible differences in the TNF-TNF receptor (TNFR) response between CHB and CHC. We studied the cytokine levels of 38 patients with CHB, 40 patients with CHC and 9 patients with dual hepatitis B and C, and compared them with the baseline levels of 12 healthy controls. The plasma levels of TNF-alpha, interferon-gamma, interleukin (IL)-2, IL-4, IL-10 and soluble TNFR-1 and 2 (sTNFR-1 and 2) were quantified by enzyme-linked immunosorbent assays. The expression of TNFR-1 and 2 in liver tissues was examined in 30 cases of CHB and 15 cases of CHC by semiquantitative reverse transcription polymerase chain reaction. The results showed that sTNFR-1 levels correlated with liver inflammation in all patients, whereas this correlation was not found with sTNFR-2 or other cytokines. Liver inflammation indicators were higher in HCV RNA+ than in HCV RNA- CHC. Most significantly, sTNFR-1 levels correlated with liver inflammation in CHB, but not in CHC. However, the expression of TNFR-1 and 2 in liver was similar between CHB and CHC. These findings suggest that the TNFR signal transduction pathway is modulated differently in HBV and HCV infection.
Tai
D I
DI
Liver Research Unit, Chang Gung Memorial Hospital and Chang Gung University, College of Medicine Taipei, Taiwan, ROC.
Tsai
S L
SL
Chen
T C
TC
Lo
S K
SK
Chang
Y H
YH
Liaw
Y F
YF
D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D019694:Hepatitis B, Chronic / Q000097:blood / Q000503:physiopathology*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000503:physiopathology*; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II
D015703:Antigens, CD; D016207:Cytokines; D017931:DNA Primers; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II