Dexamethasone lowers circulating E-selectin and ICAM-1 in healthy men

Plasma levels of circulating adhesion molecules (AMs) are increased in a nu mber of inflammatory and cardiovascular disorders. Yet the mechanisms regul ating the physiologic levels of soluble AMs are largely unknown. It has rec ently been postulated that glucocorticoids may exert their anti-inflammator y actions partially through the inhibition of cytokine-stimulated expressio n of E-selectin and intercellular adhesion molecule (ICAM-1). However, it r emains controversial whether glucocorticoids affect the basal expression of AMs on resting cells. We have thus evaluated the effects of glucocorticoid s by infusing therapeutic doses of dexamethasone (0.04 mg/kg and 1.0 mg/kg twice a day for 2 days) or placebo on plasma levels of circulating E-select in (cE-selectin), soluble thrombomodulin (sTM), circulating ICAM-1 (cICAM-1 ), and circulating vascular cell adhesion molecule (cVCAM-1) in 9 healthy m en. Plasma was obtained before infusion at 24 and 48 hours. Compared with b aseline, levels of cE-selectin decreased by 16% and 22% with the lower and the higher doses, respectively, at 48 hours (P = .007), whereas sTM was unc hanged. Both doses of dexamethasone reduced cICAM-1 by about 15% at 48 hour s (P =,007), but there were no changes in cVCAM. Dexamethasone time-depende ntly decreases plasma levels of cE-selectin and cICAM-1 in healthy men. Thi s demonstrates that a glucocorticoid-sensitive mechanism specifically down- regulates normal plasma levels of cE-selectin and clCAM-1 in healthy subjec ts, which could thus reflect minor baseline inflammation.