Fluticasone and salmeterol downregulate in vitro, fibroblast proliferationand ICAM-1 or H-CAM expression

beta (2)-adrenoreceptor agonists have pharmacological properties that may s uggest an inhibitory effect on various aspects of the inflammatory and repa ir processes that characterize asthma. Since fibroblasts express beta (2)-adrenoreceptors, the effects of differen t concentrations (0.1 - 100 nM) of fluticasone propionate (FP), salmeterol (S) and their combination (FP + S) on lung fibroblast proliferation and adh esion molecule expression were evaluated. Stimulation of human foetal lung fibroblasts with a fibrogenic cytokine, ba sic fibroblast growth factor (bFGF), resulted in a [methyl-H-3] thymidine ( [H-3]TdR) uptake, four-fold higher than that of control cultures (p = 0.000 1) and was significantly inhibited by S, at all the concentrations tested ( 0.1 - 100 nM; p < 0.05). No changes in bFGF-induced cell proliferation were observed in the presence of FP (0.1 - 100 nM; p > 0.05, all comparisons). In addition, the association FP + S did not improve the inhibitory activity of S alone (p > 0.05. each comparison). An upregulation of intercellular a dhesion molecule-1 (ICAM-1) expression was induced by tumour necrosis facto r-alpha (TNF-alpha) (p = 0.0004), but not by interleukin-4 (IL-4) (p > 0.05 ), while none of the two cytokines were able to increase hyaluronic-cellula r adhesion molecule (H-CAM) expression by lung fibroblasts (p > 0.05). A si gnificant downregulation of ICAM-1 or H-CAM expression was demonstrated in the presence of FP or S, at all concentrations, tested (0.1 - 100 nM and 10 0 nM; p < 0.01,each comparison). Interestingly, S (10 nM and 100 nM) was ab le to enhance the inhibitory activity of FP on ICAM-1 expression (p < 0.01) , but not on H-CAM expression (p > 0.1). These results show that in human foetal lung fibroblasts, fluticasone propi onate and salmeterol are effective in modulating in vitro, different lung f ibroblast biological functions that are likely to be involved in airway rem odelling.