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 tho ught to be released by a variety of cells at sites of inflammation, an d their serum levels have been used as markers of inflammatory and imm une activity. Our aim was to determine the effect of therapy with urso deoxycholic acid alone and in combination with azathioprine and predni sone on serum sICAM-1 levels in primary biliary cirrhosis. Design/meth ods: Twenty-four patients with primary biliary cirrhosis and 17 health y subjects were studied. Primary biliary cirrhosis patients received u rsodeoxycholic acid for 12 months and were then randomized in a double -blind fashion to receive prednisone and azathioprine, or placebo in a ddition to ursodeoxycholic acid. Results: sICAM-1 levels were signific antly higher in primary biliary cirrhosis patients than healthy subjec ts and fell by a median of 20% after 12 months' therapy with ursodeoxy cholic acid (P<0.0004). Addition of azathioprine and prednisone to urs odeoxycholic 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 activat ion marker, soluble interleukin-2 receptor. Conclusion: sICAM-1 levels in primary biliary cirrhosis are reduced by ursodeoxycholic acid. Fur ther reductions were achieved by adding prednisone and azathioprine. T hese reductions probably reflect an improvement in hepatobiliary excre tion and a reduction in cellular production of sICAM-1.