Dexamethasone and salbutamol stimulate human lung fibroblast proliferation

In this study, we aimed to investigate the direct effect of the drugs most frequently used in asthma, that is, glucocorticosteroids (dexamethasone) and shortacting ?2-agonists (salbutamol), on human lung fibroblast proliferation when unstimulated or activated by mast cells or eotaxin.Subconfluent human fetal lung or bronchial fibroblasts were incubated with different concentrations of the drugs (24 h) 6 activators, and [3H]-Thymidine was added (24 h) to measure their proliferation. IL-6 production in the supernatants of confluent mono-layers cultured in the presence of the drugs or forskolin (24 h) was analyzed by enzyme-linked immunosorbent assay.Both drugs alone and in the presence of the activators enhanced fibroblast proliferation in a seemingly synergistic way for both fetal and bronchial fibroblasts. Dexamethasone was found to decrease IL-6 production, while salbutamol increased it.These observations if corroborated by in vivo data may possibly account for the deleterious effect of long-term therapy with ?2-bronchodilators and inhaled glucocorticosteroids on the natural history of asthma.