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 d ense 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 immunohistochemical ly stained cryostat liver sections from 21 children with autoimmune li ver disease and from 15 children with metabolic liver disorders and hi stological evidence of portal tract inflammation as controls. Tumour n ecrosis factor-alpha and interferon-gamma producing cells were detecte d simultaneously within the inflammatory cell infiltrate in the liver biopsies of 18 patients with autoimmune liver disease, but only one pa tient with a metabolic disorder was positive for tumour necrosis facto r-alpha. There was a significant correlation between frequency of tumo ur necrosis factor-alpha and interferon-gamma producing cells, intensi ty of inflammatory cell infiltrate (p < 0.03 and p < 0.05, respectivel y) and transaminase levels (p < 0.008 and p < 0.03, respectively). The se results suggest that tumour necrosis factor-alpha and interferon-ga mma play a pathogenic role in autoimmune liver cell damage. (C) Journa l of Hepatology.