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

Abstract

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 novel T helper 1 cytokine, which augments interferon-gamma production. We designed this study to clarify the role of IL-18 in primary biliary cirrhosis and to examine whether serum IL-18 level can be a prognostic indicator for the disease. Serum IL-18 levels were measured using an enzyme linked immuno sorbent assay with mouse monoclonal antibodies. Twenty-two healthy volunteers, 31 patients with primary biliary cirrhosis (Scheuer's stage I, 13; II, 10; and IV, 8), 20 patients with autoimmune hepatitis, 11 patients with virus-related liver cirrhosis and six patients with obstructive jaundice were enrolled. Significant differences of serum IL-18 levels were observed between patients with Scheuer's stage IV and those with stage I, or II, virus-related 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, serum IL-18 levels in primary biliary cirrhosis were correlated with serum bilirubin concentrations and the Risk scores of the Mayo Clinic prognostic model for the disease. The IL-18 levels observed in patients with autoimmune hepatitis were also elevated, and correlated with the activity of the disease. These results indicate that serum interleukin-18 levels reflect the severity of primary biliary cirrhosis, the activity of autoimmune hepatitis, and may be an additive prognostic indicator in primary biliary cirrhosis.

Fig. 1

Serum IL-18 levels in healthy volunteers and patients with virus-related liver cirrhosis, obstructive jaundice and primary biliary cirrhosis (mean ± SD). Significant differences of the levels were observed between PBC patients with Scheuer's stage IV and those with I or II disease, healthy volunteers and virus-related liver cirrhosis (*P < 0·05).

Fig. 2

Changes in serum IL-18 levels in three patients with primary biliary cirrhosis. Serum IL-18 levels elevated with the increase of serum bilirubin in two out of three cases. However, the level in case 1 elevated approximately one and half years prior to the increase of serum bilirubin. LRLT, Living-related liver transplantation (✦, IL-18; ▪, total bilirubin; •, ALP).

Fig. 3

Scatter plots of serum IL-18 levels and the R scores calculated by the Mayo prognostic model in 24 PBC patients. The correlation coefficient was 0·617 (P < 0·001).

Fig. 4

Serum IL-12 (a) and IFN-gamma (b) levels in healthy volunteers and in PBC patients at various histological stages of the Scheuer's classification. Serum IFN-gamma levels were under the detection limit in the almost all patients with PBC and healthy volunteers. Regarding serum IL-12 levels, no significant differences were found between healthy volunteers and PBC patients, regardless of the stage of PBC.