To determine the intrahepatic production of tumour necrosis factor alpha (TNF alpha) in chronic liver disease three monoclonal antibodies were used against TNF alpha in immunohistochemical studies of liver tissue sections from patients with chronic liver disease. All three monoclonal antibodies stained infiltrating mononuclear cells. Monoclonal antibody II 7C2 also stained the cytoplasm or nucleus, or both, of a varied number of hepatocytes from nine patients with chronic hepatitis B virus infection, suggesting that the antigenic epitope related to hepatitis B core antigen (HBcAg) crossreacted with II7C2. The other two monoclonal antibodies, III2F3 and IV3E5, stained significantly larger numbers of mononuclear cells in cases of chronic active hepatitis B than in chronic persistent hepatitis B, or hepatitis B related liver cirrhosis. III2F3 stained significantly larger numbers of mononuclear cells in non-A, non-B chronic active hepatitis than in chronic persistent hepatitis B or hepatitis B related liver cirrhosis. These results indicate that TNF alpha is produced and secreted by infiltrating mononuclear cells in focal inflammatory areas of the liver, and suggest that TNF alpha may have a role in the inflammatory activity of chronic liver disease.
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