Increased tumor necrosis factor‐α receptor number in chronic hepatitis B virus infection

• Published in: Hepatology (Baltimore, Md.) Md.), 1991-07, Vol.14 (1), p.44-50
• Main Authors: Lau, Johnson Y. N., Sheron, Nick, Nouri‐Aria, Kayhan T., Alexander, Graeme J. M., Williams, Roger
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Carrier State - metabolism; Chronic Disease; Electrophoresis, Polyacrylamide Gel; Hepatitis B - metabolism; Human viral diseases; Humans; Infectious diseases; Medical sciences; Monocytes - metabolism; Radioimmunoassay; Receptors, Cell Surface - metabolism; Receptors, Tumor Necrosis Factor; Tumor Necrosis Factor-alpha - metabolism; Tumor Necrosis Factor-alpha - pharmacology; Viral diseases; Viral hepatitis
• ISSN: 0270-9139; 1527-3350
• DOI: 10.1002/hep.1840140108

Production of the antiviral cytokine, tumor necrosis factor‐α is increased in chronic hepatitis B virus infection, and clinical studies of tumor necrosis factor‐α have indicated a proviral effect at higher doses. To determine whether this might be related to abnormal cell surface tumor necrosis factor‐α receptor expression, binding characteristics of cell surface tumor necrosis factor‐α receptor on peripheral blood mononuclear cells in chronic hepatitis B virus carriers were studied using radioiodinated recombinant tumor necrosis factor‐α. The specific binding curves generated were analyzed according to the method of Scatchard to determine cell surface receptor numbers and dissociation constants. A single class of cell surface tumor necrosis factor‐α receptor was demonstrated on peripheral blood mononuclear cells and mononuclear subsets. The median number (range) of cell surface tumor necrosis factor‐α receptors on peripheral blood mononuclear cells from controls (n = 11), chronic hepatitis B virus patients seropositive for hepatitis B virus DNA (n = 8) and seronegative for hepatitis B virus DNA (n = 8) were 2,329 (range = 1,538 to 3,133), 3,375 (range = 2,300 to 6,718) (p < 0.01) and 3,113 (range = 2,229 to 5,246) (p < 0.05) sites/cell, respectively. They all had similar dissociation constants of 8.4 × 10−10 mol/L (range = 4.1 to 16.9), respectively. Further dissection of the peripheral blood mononuclear cells showed that this increase in cell surface receptor number was confined to the monocyte fraction (p < 0.01). Plasma tumor necrosis factor‐α levels in five patients with increased monocyte cell surface tumor necrosis factor‐α receptor numbers were also elevated. No correlation between cell surface tumor necrosis factor‐α receptor number and serum AST, HBsAg, hepatitis B virus DNA or liver histology was observed. These data indicate that cell surface tumor necrosis factor‐α receptor number is increased in monocytes but normal in lymphocytes and support previous observations that monocytes are activated in chronic hepatitis B virus infection. (HEPATOLOGY 1991;14:44–50.)