Pseudomonas aeruginosa clearance in mice: comparison of tissue, strain, and corticosteroid effects.

We used a murine model to determine whether chronic corticosteroid therapy has uniform effects on bacterial clearance processes in different tissues. After a 2-week regimen of oral prednisolone, Swiss Webster mice were challenged with Pseudomonas aeruginosa strain PAO1 or virulent derivatives of PAO1 (IP-8 and IT-10). Chronic corticosteroid therapy delayed the clearance of strain PAO1 from the peritoneal cavity. However, steroid treatment did not reduce the neutrophil influx, did not reduce the in vivo phagocytic capacity of neutrophils, and did not alter bactericidal activity of peritoneal exudate cells in vitro. Virulent isolates (IP-8 and IT-10) replicated in the peritoneal cavity in steroid-treated mice even though the neutrophil influx was similar to control mice. In contrast to the abnormal peritoneal clearance, all strains were rapidly cleared from the lungs of control and steroid-treated mice after aerosol challenge. Neutrophil influx into bronchoalveolar spaces was greater in steroid-treated mice than in control mice. All mice (control and steroid treated) survived these challenges, except for some steroid-treated mice infected intraperitoneally with IP-8. These results demonstrate that chronic steroid therapy alters bacterial clearance processes on the peritoneal surfaces to a greater extent than in the lower respiratory tract. The explanation for this altered clearance in the peritoneum is unclear, but cannot be explained by reductions in neutrophil migration to inflammatory stimuli. Therefore, the infectious risk associated with chronic corticosteroid therapy appears to depend on both the tissue and the virulence of the bacterial strain and may reflect alterations in clearance processes other than neutrophil migration.