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

The glucocorticoid budesonide and the long-acting beta(2)-adrenoceptor agon ist formoterol are used in asthma therapy for their anti-inflammatory and b ronchodilating effects, respectively. Since expression of adhesion molecule s on resident cells in the lung plays an important role in asthmatic inflam matory responses, the effects of these drugs on the cytokine-induced interc ellular 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 interleu kin (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 expressio n 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 6 4% (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 f ormoterol for VCAM-1) in a dose-dependent manner. The results show that budesonide, as well as formoterol, in probably clinic ally relevant concentrations inhibits cytokine-induced adhesion molecule ex pression on human lung fibroblasts from a concentration of 10(-9) M. This i nhibitory effect on resident cells may have implications for the infiltrati on of inflammatory cells into pulmonary tissue during therapy with these dr ugs in asthma.