Submitted to: Annual North American Cystic Fibrosis Conference
Publication Type: Abstract Only
Publication Acceptance Date: 7/12/2000
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 Group 1 (n = 1) and Group 2 (n = 2) received 10 ml of diluent via fiberoptic bronchoscopy. Lambs in Groups 3 (n = 3) and 4 (n = 3) received 10 ml diluent containing 2.5 X 10**8 CFU/ml M. haemolytica. At 24 hr post inoculation (PI), lambs in Groups 2 and 4 received 10 ml diluent containing 0.5 mg/ml H-DDDDDDD-OH, and lambs in Groups 1 and 3 only received 10 ml diluent. Lambs in Group 5 (n = 3) and 7 (n = 3) received 10 ml diluent containing 0.5 mg/ml H-DDDDDDD-OH and, lambs in Group 6 (n = 3) 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 from the inoculation site for histopathology and quantitative bacterial culture. Overall, H-DDDDDDD-OH alone was well tolerated and did not induce any significant changes. A single dose of H-DDDDDDD-OH (5.0 mg) reduced pulmonary inflammation and the concentration of M. haemolytica in infected lung tissue. Administration of H-DDDDDDD-OH after infection was more effective in reducing the consolidation and lesion scores at the deposition site than administration of H-DDDDDDD-OH 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 H-DDDDDDD-OH therapy.