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Title: EFFICACY OF SMAP29 IN AN OVINE MODEL OF PULMONARY INFECTION AND ITS POTENTIAL FOR TREATING P. AERUGINOSA INFECTION IN PATIENTS WITH CYSTIC FIBROSIS

Author
item BROGDEN, KIM
item KALFA, V - VISITING SCIENTIST,TURKEY
item ACKERMANN, M - IOWA STATE UNIV.,AMES,IA.
item MCCRAY, JR., P - UNIV.OF IOWA,IOWA CITY,IA
item TACK, B - UNIV.OF IOWA,IOWA CITY,IA

Submitted to: Annual North American Cystic Fibrosis Conference
Publication Type: Abstract Only
Publication Acceptance Date: 7/7/1999
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: SMAP29 is a sheep myeloid cathelicidin antimicrobial peptide efficacious against Pseudomonas aeruginosa in vitro. To assess its efficacy in treating respiratory infections in vivo, we established a homologous ovine model using SMAP29 against the ovine respiratory pathogen Pasteurella haemolytica. Lambs were randomized and 5 lambs received vehicle (10 ml PBS containing 0.25 mg surfactant/ml) into the of the right lung (pulmonary deposition site) via fiberoptic bronchoscopy and 10 lambs received 10 ml vehicle containing 2.5 X 108 CFU P haemolytica/ml. 24 hours post infection (PI), the 5 lambs previously receiving vehicle were again randomized and 2 lambs received an additional 10 ml vehicle and 3 lambs received 10 ml vehicle containing SMAP29. The 10 lambs previously receiving P haemolytica were also randomized and 5 lambs received an additional 10 ml vehicle. The other 5 lambs received 10 ml vehicle containing 50 ug SMAP29/ml (total dose, 0.5 mg). At 48 hrs PI, all lambs were euthanized. Pulmonary tissues and bronchoalveolar lavage (BAL) fluids were collected. Overall, vehicle and vehicle containing SMAP29 alone were well tolerated and did not induce any significant changes. In infected lambs, SMAP29 reduced the concentration of bacteria in both the BAL fluid (3.77 log10 CFU/ml in the infected group vs. 1.73 log10 CFU/ml in the SMAP2 treated group) and consolidated pulmonary tissues (5.08 log10 CFU/ml in the infected group vs. 3.70 log10 CFU/ml in the SMAP29 treated group) at the deposition site. In conclusion, a single dose of SMAP29 significantly reduced the concentration of bacteria in this model of infection. Antimicrobial peptides such as SMAP29 may have applications in the treatment or prevention of pulmonary infection.