Inhibitory capacity of different steroids on neutrophil migration across a bilayer of endothelial and bronchial epithelial cells

Neutrophil infiltration to the airway lumen is a common feature of respiratory inflammatory processes. The aim of this study was to evaluate whether different corticosteroids exert any selective effect on the migration of isolated neutrophils. A bilayer of cultured human endothelial and bronchial epithelial cells was used as a model for neutrophil migration through the blood-air barrier. Low spontaneous migration of neutrophils (2.8 +/- 0.9%, n = 8; mean +/- S.E.M.) occurred, while in the absence of any steroid, a migration of 28.5 +/- 7.6% could be induced by lipopolysaccharide. Pre-incubation during I h of epithelial cells with dexamethasone, budesonide, or prednisolone (10(-10)-10(-4) M) showed in all instances a concentration-dependent inhibition following a bell-shaped curve. At 10(-7) M, both dexamethasone and budesonide were on the minimum effect peak of the bell-shaped curve. The peak for prednisolone was found at 10(-8) M. However, when steroid pre-incubation was extended to 4 h, a sigmoid curve was observed, with significant inhibition of migration at concentrations >10(-7) M. Steroids can inhibit neutrophil recruitment through two different pathways with distinct result, depending on the length of incubation time. (C) 2003 Elsevier B.V. All rights reserved.