CELLULAR EXPRESSION OF TUMOR-NECROSIS-FACTOR-ALPHA AND INTERFERON-GAMMA IN THE LIVER BIOPSIES OF CHILDREN WITH CHRONIC LIVER-DISEASE

The liver biopsies of patients with autoimmune liver diseases have a dense portal tract mononuclear cell infiltrate. To investigate whether these cells produce tumour necrosis factor-alpha and interferon-gamma, cytokines which could be involved in the autoimmune attack through a direct cytopathic effect and/or through induction/enhancement of major histocompatibility complex antigen expression, we immunohistochemically stained cryostat liver sections from 21 children with autoimmune liver disease and from 15 children with metabolic liver disorders and histological evidence of portal tract inflammation as controls. Tumour necrosis factor-alpha and interferon-gamma producing cells were detected simultaneously within the inflammatory cell infiltrate in the liver biopsies of 18 patients with autoimmune liver disease, but only one patient with a metabolic disorder was positive for tumour necrosis factor-alpha. There was a significant correlation between frequency of tumour necrosis factor-alpha and interferon-gamma producing cells, intensity of inflammatory cell infiltrate (p < 0.03 and p < 0.05, respectively) and transaminase levels (p < 0.008 and p < 0.03, respectively). These results suggest that tumour necrosis factor-alpha and interferon-gamma play a pathogenic role in autoimmune liver cell damage. (C) Journal of Hepatology.