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Toxicologic Pathology, Vol. 28, No. 2,
317-325 (2000)
DOI: 10.1177/019262330002800212
Nedocromil Sodium Inhibits Canine Adenovirus Bronchiolitis in Beagle Puppies
Kurt A. Anderson
Department of Pediatrics, Steele Memorial Children's Research Center, Department of Pediatrics, Respiratory Sciences Center, and Department of Cell Biology and Anatomy, University of Arizona, Tucson, Arizona 85724
Richard J. Lemen
Department of Pediatrics, Steele Memorial Children's Research Center, Department of Pediatrics, Respiratory Sciences Center, and Department of Cell Biology and Anatomy, University of Arizona, Tucson, Arizona 85724, rlemen{at}umcaz.edu
Natalie S. Weger
Department of Pediatrics, Steele Memorial Children's Research Center, Department of Pediatrics, Respiratory Sciences Center, and Department of Cell Biology and Anatomy, University of Arizona, Tucson, Arizona 85724
Huizhong Chen
Department of Pediatrics, Steele Memorial Children's Research Center, Department of Pediatrics, Respiratory Sciences Center, and Department of Cell Biology and Anatomy, University of Arizona, Tucson, Arizona 85724
Mark C. Bowers
Department of Pediatrics, Steele Memorial Children's Research Center, Department of Pediatrics, Respiratory Sciences Center, and Department of Cell Biology and Anatomy, University of Arizona, Tucson, Arizona 85724
Mark L. Witten
Department of Pediatrics, Steele Memorial Children's Research Center, Department of Pediatrics, Respiratory Sciences Center, and Department of Cell Biology and Anatomy, University of Arizona, Tucson, Arizona 85724
R. Clark Lantz
Department of Pediatrics, Steele Memorial Children's Research Center, Department of Pediatrics, Respiratory Sciences Center, and Department of Cell Biology and Anatomy, University of Arizona, Tucson, Arizona 85724
David E. Bice
The Lovelace Respiration Institute, Albuquerque, New Mexico 87111
Bruce A. Muggenburg
The Lovelace Respiration Institute, Albuquerque, New Mexico 87111
Nedocromil sodium is a nonsteroidal anti-inflammatory drug used to control asthmatic attacks. Our hypothesis is that nedocromil sodium inhibits virus-induced airway inflammation, a common trigger of asthma. We nebulized nedocromil sodium into beagle dogs (n = 10, mean ± SEM ages: 149 ± 13 days) before and after inoculation with canine adenovirus type 2 (CAV2). Control dogs (n = 10) received saline aerosols and were either infected with CAV2 (Sa1/CAV2, n = 7, mean ± SEM ages: 140 ± 11 days) or were not infected (Sal/Sal, n = 3, ages: 143 ± 0 days). All dogs were anesthetized with choralose (80 mg/kg IV), intubated, and mechanically ventilated. Pulmonary function tests and bronchoalveolar lavage (BAL) were performed using standard techniques. Pulmonary function tests revealed no significant change between the nedocromil sodium and non-nedocromil-treated groups. The percentage of infected bronchioles was quantitated as the number of inflamed airways of 40 bronchioles examined times 100 for each dog. Nedocromil-treated dogs had significantly (p < 0.05) less mucosal inflammation (mean ± SEM, 39% ± 5%), epithelial denudation (36% ± 5%), and BAL neutrophilia (11 ± 3) than did Sal/CAV2 dogs (51% ± 6%, 57% ± 4%, and 33% ± 8%, respectively). We concluded that pretreatment with nedocromil sodium aerosols attenuated CAV2-induced airway inflammation in these beagle puppies.
Key Words: Nedocromil sodium • bronchiolitis • viral infections • inflammation • pulmonary function
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