CIRCULATING PROINFLAMMATORY CYTOKINES (IL-1-BETA, TNF-ALPHA, AND IL-6) AND IL-1 RECEPTOR ANTAGONIST (IL-1RA) IN FULMINANT HEPATIC-FAILURE AND ACUTE HEPATITIS

Fulminant hepatic failure (FHF) is characterized by massive necroinfla mmation of the liver tissue and is associated with high mortality. Ser um concentrations of IL-1 beta, tumour necrosis factor-alpha (TNF-alph a), IL-6 and IL-1 receptor antagonist (IL-1Ra) were measured in 30 pat ients with FHF and in 23 patients with acute hepatitis (AH) before sta rt of treatment and in 23 healthy controls. Levels of all four molecul es were increased significantly in FHF compared with AH, in which valu es were higher than in the healthy controls. High serum levels of IL-1 beta and a significantly reduced ratio of IL-1Ra to IL-1 beta (IL-1Ra /IL-1 beta) were observed in FHF patients who subsequently died compar ed with subjects who survived. TNF-alpha and IL-6 concentrations were correlated with levels of human hepatocyte growth factor (hHGF), an in dex of hepatocyte regeneration. Although serum cytokine levels varied considerably between patients within each group studied, it is suggest ed that the striking elevation in proinflammatory cytokine levels in F HF may reflect both the insufficiency of hepatitis virus elimination a nd a failure to control a vicious cytokine cascade leading to overwhel ming hepatocyte destruction rather than regeneration. The high cytokin e levels observed in these patients and the significantly elevated IL- 1Ra/IL-1 beta ratio in FHF patients who survived compared with those w ho did not suggest the possible therapeutic use of cytokine antagonist s for the control of this life-threatening disease.