Effects of antirheumatic drugs on adhesiveness of endothelial cells and neutrophils

Because disease-modifying antirheumatic drugs might exert part of their eff ects on adhesion of polymorphonuclear neutrophils (PMN) to endothelial cell s, this being the first step for PMN migration to inflammatory lesions, we evaluated such drug effects in vitro. Gold sodium thiomalate (GSTM) impaire d the ability of interleukin 1 beta (IL-1 beta)-stimulated human umbilical vein endothelial cells (HUVEC) to express E-selectin and to bind PMN but ha d no effect on the expression of intercellular adhesion molecule 1 (ICAM-1) or on hyperadhesivity of N-formyl-methionyl-leucyl-phenylalanine (fMLP)-st imulated PMN. Auranofin (AF) interacted with HUVEC and PMN adhesiveness but in opposite directions: this drug hampered IL-1 beta-induced HUVEC hyperad hesiveness and expression of E-selectin and intercellular adhesion molecule 1, but augmented PMN adherence and CD18 expression. The net effect of aura nofin was a reduction of cytokine-driven adhesiveness and enhancement of fo rmylpeptide-induced adhesion. Salazopyrin did not affect HUVEC or PMN adhes iveness or E-selectin and intercellular adhesion molecule 1 expression. Thu s, the gold-containing drugs modulated HUVEC and PMN adhesiveness by differ ent mechanisms but ones involving surface adhesion molecules. BIOCHEM PHARM ACOL 56;12:1661-1669, 1998. (C) 1998 Elsevier Science Inc.