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

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Abstract
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.)