IMPAIRED LIPOPOLYSACCHARIDE-INDUCIBLE TUMOR-NECROSIS-FACTOR PRODUCTION INVITRO BY PERIPHERAL-BLOOD MONOCYTES OF PATIENTS WITH VIRAL-HEPATITIS

We investigated lipopolysaccharide‐induced tumor necrosis factor production in vitro by peripheral blood monocytes from patients with various liver diseases. Tumor necrosis factor production was found to be significantly reduced in patients with chronic hepatitis B (n = 17; 135 ± 30 pg tumor necrosis factor/ml; mean ± S.E.M.) and patients with chronic non‐A, non‐B hepatitis (n = 15; 212 ± 22 pg tumor necrosis factor/ml) compared with healthy control individuals (n = 47; 411 ± 40 pg tumor necrosis factor/ml; p < 0.0005 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 ± 81 pg tumor necrosis factor/ml) and alcohol‐induced fatty liver changes (n = 5; 401 ± 62 pg tumor necrosis factor/ml) produced normal amounts of tumor necrosis 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 ± 32 pg/ml) or non‐A, non‐B hepatitis (n = 13; 97 ± 16 pg/ml) could not be induced to produce more tumor necrosis factor either when prestimulated with γ‐interferon (170 ± 45 pg/ml and 149 ± 32 pg/ml, respectively), a lymphokine known to activate monocytes, or with the cyclooxygenase inhibitor indomethacin to reduce the suppressive effect of prostaglandin E2 (148 ± 40 pg/ml and 153 ± 45 pg/ml, respectively). In contrast, patients with alcoholic cirrhosis (n = 11; 178 ± 31 ng tumor necrosis factor/ml) showed significant increase of tumor necrosis factor production by lipopolysaccharide‐stimulated monocytes when prestimulated with γ‐interferon (n = 11; 395 ± 80 pg tumor necrosis factor/ml; p < 0.025) or indomethacin (n = 11; 393 ± 82 pg tumor necrosis factor/ml; p < 0.05). A significant reduction in lipopolysaccharide‐induced tumor necrosis factor production by peripheral blood monocytes was observed in acute hepatitis B but not in acute hepatitis A or non‐A, non‐B hepatitis. These investigations suggest that lipopolysaccharide‐induced tumor necrosis factor production by peripheral blood monocytes is impaired in patients with chronic viral hepatitis and acute hepatitis B. (HEPATOLOGY 1990;12:1118–1124). Copyright © 1990 American Association for the Study of Liver Diseases