Dexamethasone lowers circulating E-selectin and ICAM-1 in healthy men.
Plasma levels of circulating adhesion molecules (AMs) are increased in a number of inflammatory and cardiovascular disorders. Yet the mechanisms regulating the physiologic levels of soluble AMs are largely unknown. It has recently been postulated that glucocorticoids may exert their anti-inflammatory actions partially through the inhibition of cytokine-stimulated expression of E-selectin and intercellular adhesion molecule (ICAM-1). However, it remains controversial whether glucocorticoids affect the basal expression of AMs on resting cells. We have thus evaluated the effects of glucocorticoids 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-selectin (cE-selectin), soluble thrombomodulin (sTM), circulating ICAM-1 (cICAM-1), and circulating vascular cell adhesion molecule (cVCAM-1) in 9 healthy men. Plasma was obtained before infusion at 24 and 48 hours. Compared with baseline, 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 unchanged. Both doses of dexamethasone reduced cICAM-1 by about 15% at 48 hours (P = .007), but there were no changes in cVCAM. Dexamethasone time-dependently decreases plasma levels of cE-selectin and cICAM-1 in healthy men. This demonstrates that a glucocorticoid-sensitive mechanism specifically down-regulates normal plasma levels of cE-selectin and cICAM-1 in healthy subjects, which could thus reflect minor baseline inflammation.
Jilma
B
B
Department of Clinical Pharmacology-TARGET, Vienna University Hospital School of Medicine, Austria.
Blann
A D
AD
Stohlawetz
P
P
Eichler
H G
HG
Kautzky-Willer
A
A
Wagner
O F
OF
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D018592:Cross-Over Studies; D003907:Dexamethasone / Q000494:pharmacology*; D004311:Double-Blind Method; D015536:Down-Regulation / Q000187:drug effects; D019040:E-Selectin / Q000097:blood*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D008297:Male; D018180:Thrombomodulin / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
D000893:Anti-Inflammatory Agents; D019040:E-Selectin; D005938:Glucocorticoids; D018180:Thrombomodulin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D003907:Dexamethasone