EFFECT OF GOLD SODIUM THIOMALATE AND ITS THIOMALATE COMPONENT ON THE IN-VITRO EXPRESSION OF ENDOTHELIAL-CELL ADHESION MOLECULES

Endothelial adhesion molecules play an important role in the tissue re cruitment of leukocytes in inflammatory conditions such as rheumatoid arthritis. We have investigated the effect of the antirheumatic drug g old sodium thiomalate on adhesion molecule protein and mRNA expression in cultured human endothelial cells. Gold sodium thiomalate inhibited cytokine (TNF, IL-1, IL-4)-stimulated expression of vascular cell adh esion molecule-1 and E-selectin but not intercellular adhesion molecul e-1 on endothelial cells. Gold sodium thiomalate also suppressed TNF-s timulated increases in vascular cell adhesion molecule-1 and E-selecti n mRNA levels but had no effect on intercellular adhesion molecule-1 m RNA. Thiomalate (mercaptosuccinate), but not gold thioglucose or D-pen icillamine, mimics the effect of gold sodium thiomalate at equimolar c oncentrations. We propose that the inhibition of vascular cell adhesio n molecule-1 and E-selectin expression by gold sodium thiomalate is du e to its thiomalate and not its gold component. Gold sodium thiomalate has a direct effect on endothelial adhesion molecule expression, and this may contribute to its antiinflammatory activity.