Serum interferon-gamma-inducing factor/IL-18 levels in primary biliary cirrhosis

Primary biliary cirrhosis is an autoimmune disease of the liver in which T helper 1 cytokines predominate over those of T helper 2 in the pathogenesis . Interleukin-18 (IL-18), for which the gene was recently cloned, is a nove l T helper 1 cytokine, which augments interferon-gamma production. We desig ned this study to clarify the role of IL-18 in primary biliary cirrhosis an d to examine whether serum IL-18 level can be a prognostic indicator for th e disease. Serum IL-18 levels were measured using an enzyme linked immuno s orbent assay with mouse monoclonal antibodies. Twenty-two healthy volunteer s, 31 patients with primary biliary cirrhosis (Scheuer's stage I, 13; II, 1 0; and IV, 8), 20 patients with autoimmune hepatitis, 11 patients with viru s-related liver cirrhosis and six patients with obstructive jaundice were e nrolled. Significant differences of serum IL-18 levels were observed betwee n patients with Scheuer's stage IV and those with stage I, or II, virus-rel ated liver cirrhosis and obstructive jaundice (P < 0.05). The IL-18 levels in primary biliary cirrhosis increased according to the disease progression , and fell promptly after living-related liver transplantation. Moreover, s erum IL-18 levels in primary biliary cirrhosis were correlated with serum b ilirubin concentrations and the Risk scores of the Mayo Clinic prognostic m odel for the disease. The IL-18 levels observed in patients with autoimmune hepatitis were also elevated, and correlated with the activity of the dise ase. These results indicate that serum interleukin-18 levels reflect the se verity of primary biliary cirrhosis, the activity of autoimmune hepatitis, and may be an additive prognostic indicator in primary biliary cirrhosis.