G551D CF mice display an abnormal host response and have impaired clearance of Pseudomonas lung disease

Several cystic fibrosis (CF) mouse models demonstrate an increased suscepti bility to Pseudomonas aeruginosa lung infection, characterized by excessive inflammation and high rates of mortality. Here we developed a model of chr onic P. aeruginosa lung disease in mice homozygous for the murine CF transm embrane conductance regulator G551D mutation that provides an excellent mod el for CF lung disease. After 3 days of infection with mucoid P. aeruginosa entrapped in agar beads, the G551D animals lost substantially more body we ight than non-CF control animals and were less able to control the infectio n, harboring over 40-fold more bacteria in the lung. The airways of infecte d G551D animals contained altered concentrations of the inflammatory mediat ors tumor necrosis factor-alpha, KC/N51, and macrophage inflammatory protei n-2 during the first 2 days of infection, suggesting that an ineffective in flammatory response is partly responsible for the clearance defect.