Effect of fluticasone propionate and salmeterol on Pseudomonas aeruginosa infection of the respiratory mucosa in vitro

The purpose of this study was to investigate the effect of the corticosteroid, fluticasone propionate (FP), on Pseudomonas aeruginosa infection of the respiratory mucosa of an organ culture model in vitro. Organ cultures infected with P. aeruginosa had significantly (p less than or equal to 0.05) elevated levels of mucosal damage and significantly (p less than or equal to 0.05) less ciliated cells compared to controls. Preincubation of tissue with FP (10(-6) or 10(-5) but not 10(-7) NZ) prior to P. aeruginosa infection significantly (p less than or equal to 0.05) reduced the bacterially induced mucosal damage in a concentration-dependent manner. PP (10(-5) M) also significantly (p less than or equal to 0.05) prevented loss of ciliated cells. FP did not alter the density of bacteria adherent to the different mucosal features of the organ cultures, but did reduce total bacterial numbers due to the reduced amount of damaged tissue, which is a preferred site of P. aeruginosa adherence. It has previously been shown that the long-acting beta(2)-agonist salmeterol (4 x 10(-7) M) also reduces the mucosal damage caused by P. aeruginosa infection, probably via elevation of intracellular cyclic adenosine monophosphate concentrations. Preincubation of tissue with both 10(-7) M FP and 10(-7) M salmeterol, concentrations at which they did not by themselves influence the effect of P. aeruginosa infection, significantly (p less than or equal to 0.05) reduced P. aeruginosa-induced loss of cilia. However, there was no additional benefit from adding 4x10(-7) M salmeterol to 10(-6) M FP. In conclusion fluticasone propionate reduced mucosal damage caused by P. aeruginosa infection in vitro and preserved ciliated cells. There was a synergistic action with salmeterol in the preservation of ciliated cells.