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 corticostero id, 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 o r equal to 0.05) elevated levels of mucosal damage and significantly (p les s than or equal to 0.05) less ciliated cells compared to controls. Preincub ation of tissue with FP (10(-6) or 10(-5) but not 10(-7) NZ) prior to P. ae ruginosa 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 los s of ciliated cells. FP did not alter the density of bacteria adherent to t he different mucosal features of the organ cultures, but did reduce total b acterial numbers due to the reduced amount of damaged tissue, which is a pr eferred site of P. aeruginosa adherence. It has previously been shown that the long-acting beta(2)-agonist salmetero l (4 x 10(-7) M) also reduces the mucosal damage caused by P. aeruginosa in fection, probably via elevation of intracellular cyclic adenosine monophosp hate concentrations. Preincubation of tissue with both 10(-7) M FP and 10(- 7) M salmeterol, concentrations at which they did not by themselves influen ce the effect of P. aeruginosa infection, significantly (p less than or equ al 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. ae ruginosa infection in vitro and preserved ciliated cells. There was a syner gistic action with salmeterol in the preservation of ciliated cells.