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


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 months' 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.


CONCLUSIONS
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.
Lim
A G
AG
Division of Biochemical Medicine, St George's Hospital Medical School, London, UK.
Wolfhagen
F H
FH
Verma
A
A
van Buuren
H R
HR
Jazrawi
R P
RP
Levy
J H
JH
Northfield
T C
TC
Schalm
S W
SW
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001379:Azathioprine / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy* / Q000276:immunology*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use*; D015375:Receptors, Interleukin-2 / Q000097:blood; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D002756:Cholagogues and Choleretics; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D018799:Intercellular Adhesion Molecule-1; D014580:Ursodeoxycholic Acid; D001379:Azathioprine; D011241:Prednisone