We investigated lipopolysaccharide-induced tumor necrosis factor production in uitro by peripheral blood monocytee from patients with various liver diseases.
Tumor necrosis factor production was found to be significantlyreduced in patients with chronic hepatitis B (n = 17; 136 f 30 pg tumor necrosis factor/ml; mean f S.E.M.) and patients with chronic non-A, non-B hepatitis (n = 16; 212 * 22 pg tumor necrosis factor/ml) compared with healthy control individuals (n = 47; 411 f 40 pg tumor necrosis factor/ml; p < 0.0006 and p < 0.01, respectively). This reduced tumor necrosis factor production was not only seen with an optimal stimulating concentration of lipopolysaccharide (100 ng/ml) but also with suboptimal concentrations (0.1 ng/ml). In contrast to patients with chronic viral hepatitis, monocytes from patients with alcohol-induced cirrhosis (n = 26; 444 * 49 pg tumor necrosis factor/ml), primary biliary cirrhosis (n = 7; 412 f 81 pg tumor necrosis factor/ml) and alcoholinduced fatty liver changes (n = 6; 401 * 62 pg tumor necroeie factorlml) produced normal amounts of tumor necroeie factor when stimulated with an optimal concentration of lipopolysaccharide. Lipopolysaccharide (0.1 ng lipopolysaccharide/ml)-stimulated peripheral blood monocytes of patients with chronic hepatitis B (n = 15; 102 f 32 pg/ml) or non-A, non-B hepatitis (n = 13; 97 f 16 pg/ml) could not be induced to produce more tumor necrosis factor either when prestimulated with y-interferon (170 f 46 pg/ml and 149 f 32 pg/ml, respectively), a lymphokine known to activate monocytes, or with the cyclooxygenase inhibitor indomethacin to reduce the suppressive effect of prostaglandin E, (148 * 40 pg/ml and 163 * 46 pg/ml, respectively). In contrast, patients with alcoholic cirrhosis (n = 11; 178 31 ng tumor necrosis factor/ml) showed signi5cant increase of tumor necrosis factor production by lipopolysaccharide-stimulated monocytes when prestimulated with y-interferon (n = 11; 396 f 80 pg tumor necrosis factor/ml; p < 0.025) or indomethacin (n = 11; 393 * 82 pg tumor necrosis