Aerosolized prolastin suppresses bacterial proliferation in a model of chronic Pseudomonas aeruginosa lung infection

High levels of active neutrophil elastase (HNE) are present in the respirat ory secretions of patients with cystic fibrosis (CF). We hypothesized that aerosolized Prolastin (alpha(1)-protease inhibitor or alpha(1)PI, purified from human blood) could suppress airway neutrophil inflammation and acceler ate bacterial clearance from the lung in a model of chronic Pseudomonas aer uginosa lung infection. Because human alpha(1)PI effectively inhibits rat a s well as human neutrophil elastase (NE) activity in vitro, we choose to te st this hypothesis using a rat agar bead model of chronic P. aeruginosa lun g infection. In this model, aerosolized Prolastin significantly decreased e lastase activity (p < 0.01), lung neutrophil counts (p < 0.01), and bacteri al colony counts (p < 0.01). Prolastin had no direct bactericidal effect on P. aeruginosa in vitro. Lung tissue histopathology revealed a marked decre ase in lung inflammation in animals treated with Prolastin. These studies i ndicate that Prolastin can significantly decrease the elastase burden in th e chronically infected lung. In addition, not only does Prolastin suppress lung inflammation, but it also markedly decreases P. aeruginosa density in a rat model of chronic P. aeruginosa lung infection. These data suggest tha t aerosolized alpha(1)PI may represent a useful nonantibiotic adjunct in th e treatment and control of infection and inflammation associated with CF lu ng disease.