Reversal of persistent postbronchiolitis airway abnormalities with dexamethasone in rats.
Viral bronchiolitis is a common disease that may result in persistent airway abnormalities. Previous studies of neonatal bronchiolitis in rats revealed chronic sequelae, including airway obstruction, airway hyperresponsiveness, increased production of airway eicosanoids, and increased numbers of bronchiolar mast cells. To address the hypothesis that postbronchiolitis airway obstruction is caused in part by reversible processes, we tested whether obstruction could be reversed by a brief course of high-dose corticosteroids. Neonatal Brown Norway rats (5 days of age) were inoculated with parainfluenza type 1 virus or sterile vehicle. At 8 wk of age, rats were treated with dexamethasone (1.4 mg.kg-1 x day-1 sc) or saline for 3 days and were evaluated for lung mechanics, gas exchange, and lung inflammatory cells 1 day after the last injection. Dexamethasone normalized the chronic virus-induced airway obstruction and reduced the numbers of bronchiolar mast cells and other inflammatory cells. Resistance and dynamic compliance correlated significantly with bronchiolar mast cells but not with other airway inflammatory cell infiltrates. We conclude that the airway abnormalities that persist in rats after recovery from neonatal bronchiolitis are associated with increased numbers of bronchiolar mast cells and are largely due to corticosteroid-sensitive mechanisms.
Sheth
K K
KK
Department of Medicine, University of Wisconsin School of Medicine, Madison.
Sorkness
R L
RL
Clough
J J
JJ
McAllister
P K
PK
Castleman
W L
WL
Lemanske
R F
RF
D000403:Airway Resistance / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001990:Bronchiolitis, Viral / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D003907:Dexamethasone / Q000627:therapeutic use*; D005260:Female; D006632:Histamine / Q000097:blood; D008168:Lung / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000502:physiology; D010100:Oxygen / Q000097:blood; D010222:Parainfluenza Virus 1, Human; D018184:Paramyxoviridae Infections / Q000473:pathology; D011247:Pregnancy; D011659:Pulmonary Gas Exchange / Q000502:physiology; D051381:Rats; D011914:Rats, Inbred BN
D003907:Dexamethasone; D006632:Histamine; D010100:Oxygen