Budesonide and formoterol inhibit ICAM-1 and VCAM-1 expression of human lung fibroblasts

Abstract

The glucocorticoid budesonide and the long-acting beta(2)-adrenoceptor agonist formoterol are used in asthma therapy for their anti-inflammatory and bronchodilating effects, respectively. Since expression of adhesion molecules on resident cells in the lung plays an important role in asthmatic inflammatory responses, the effects of these drugs on the cytokine-induced intercellular adhesion molecule-1 (ICAM)-1 and vascular cell adhesion molecule-1 (VCAM)-1 expression of human lung fibroblasts were investigated. Budesonide and formoterol were added in the absence or presence of interleukin (1L)-1 beta, tumour necrosis factor-alpha (TNF-alpha), interferon gamma (IFN-gamma) or IT-4 to human lung fibroblasts; ICAM-1 and VCAM-1 expression were measured after 8 h using a cell surface enzyme linked immunosorbent assay (ELISA). It was found that both budesonide and formoterol significantly inhibited (p<0.05) the increased expression of ICAM-1 and VCAM-1 after stimulation with IL-1 beta (maximal inhibition (median (25-75% percentiles) 50 (48-52) and 61% (42-69), respectively, with budesonide and 55 (50-73) and 86% (64-94), respectively, with formoterol (10(-7) M)), TNF-alpha (maximal inhibition 49 (46-57) and 57% (44-68), respectively, with budesonide and 44 (40-75) and 62% (52-83) respectively, with formoterol), IFN-gamma (maximal inhibition 64% (41-67) with budesonide and 39% (29-49) with formoterol for ICAM-1) and IL-4 (maximal inhibition 82% (69-92) with budesonide and 43% (33-67) with formoterol for VCAM-1) in a dose-dependent manner. The results show that budesonide, as well as formoterol, in probably clinically relevant concentrations inhibits cytokine-induced adhesion molecule expression on human lung fibroblasts from a concentration of 10(-9) M. This inhibitory effect on resident cells may have implications for the infiltration of inflammatory cells into pulmonary tissue during therapy with these drugs in asthma.