Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 9/6/2000
Publication Date: N/A
Technical Abstract: The in vitro effectiveness of AP suggests it may have application in the treatment or prevention of pulmonary infection. To test this, we established a model of acute pneumonia in lambs using M. haemolytica. Lambs in Groups 1 and 2 received 10 ml of diluent. Lambs in Groups 3 and 4 received 10 ml diluent containing 2.5 X 108 CFU/ml M. haemolytica. 24 hr PI, lambs in Groups 2 and 4 received 10 ml diluent containing 0.5 mg/ml AP and lambs in Groups 1 and 3 only received 10 ml diluent. Lambs in Groups 5 and 7 received 10 ml diluent containing 0.5 mg/ml H-DDDDDDD-OH, and lambs in Group 6 received 10 ml diluent. At 24 hr PI, lambs in Group 5 received 10 ml diluent, and lambs in Groups 6 and 7 received 10 ml diluent containing 2.5 X 10**8 CFU/ml M. haemolytica. At 48 hr PI, all lambs were euthanized and tissues were collected for histopathology and quantitative bacterial culture. Overall, AP alone was well tolerated and did not induce eany significant changes. A single dose of AP (5.0 mg) reduced pulmonary inflammation, and the concentration of M. haemolytica in infected lung tissue. Administration of AP after infection was more effective in reducing the consolidation and lesion scores at the deposition site than administration of AP prior to infection (P< or = 0.02). In conclusion, the in vivo effectiveness of AP suggests it may have applications in the treatment of pulmonary infections. Further studies are needed to confirm these findings and also to determine the optimal doses and intervals of AP therapy. This research was supported in part by the Cystic Fibrosis Foundation.