Soluble intercellular adhesion molecule-1 in primary biliary cirrhosis: effect of ursodeoxycholic acid and immunosuppressive therapy

OBJECTIVES:Soluble intercellular adhesion molecule-1 (sICAM-1) is thought to be released by a variety of cells at sites of inflammation, and their serum levels have been used as markers of inflammatory and immune activity. Our aim was to determine the effect of therapy with ursodeoxycholic acid alone and in combination with azathioprine and prednisone on serum sICAM-1 levels in primary biliary cirrhosis. DESIGN/METHODS:Twenty-four patients with primary biliary cirrhosis and 17 healthy subjects were studied. Primary biliary cirrhosis patients received ursodeoxycholic acid for 12 months and were then randomized in a double-blind fashion to receive prednisone and azathioprine, or placebo in addition to ursodeoxycholic acid. RESULTS:sICAM-1 levels were significantly higher in primary biliary cirrhosis patients than healthy subjects and fell by a median of 20% after 12 monthsʼ therapy with ursodeoxycholic acid (P < 0.0004). Addition of azathioprine and prednisone to ursodeoxycholic acid resulted in a further reduction of sICAM-1 levels by a median of 25% (P < 0.01). Reductions in sICAM-1 were accompanied by improvement in liver function tests but not in the lymphocyte activation marker, soluble interleukin-2 receptor. CONCLUSION:sICAM-1 levels in primary biliary cirrhosis are reduced by ursodeoxycholic acid. Further reductions were achieved by adding prednisone and azathioprine. These reductions probably reflect an improvement in hepatobiliary excretion and a reduction in cellular production of sICAM-1.