Effects of dexamethasone on acute virus-induced airway dysfunction in adult rats.
Respiratory viral infections have been associated with airway obstruction and hyperresponsiveness, and exacerbations of asthma. Although virus-induced asthma is thought to be precipitated by airway inflammation, the clinical efficacy and rationale for using antiinflammatory treatment during such exacerbations remains controversial. The purpose of this study was to use a well characterized animal model of respiratory viral illness to test the hypothesis that the inflammatory response to viral infection is responsible for the development of airway dysfunction. Adult rats were inoculated with either Sendai virus or sterile vehicle and treated with daily injections of dexamethasone or saline. At postinoculation d 4, 5, or 6, rats were evaluated for airway obstruction, hyperresponsivenes, inflammation, and lung viral titers. Saline-treated infected rats had significant airway obstruction (increased resistance, decreased dynamic compliance), hyperresponsiveness (i.v. methacholine), and inflammation (increased bronchoalveolar lavage leukocytes) compared with noninfected controls. In contrast, dexamethasone-treated infected rats had no increase in bronchoalveolar lavage leukocytes and significantly smaller changes in airway physiology, but had increased lung viral titers compared with saline-treated infected rats. We conclude that glucocorticoid suppression of the inflammatory response to respiratory viral infection largely prevents virus-associated airway dysfunction.
Mehta
H
H
Department of Medicine, University of Wisconsin, Madison 53792-3244, USA.
Sorkness
R
R
Kaplan
M R
MR
Castleman
W L
WL
Lemanske
R F
RF
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003907:Dexamethasone / Q000494:pharmacology*; D007249:Inflammation; D007962:Leukocytes / Q000473:pathology; D008168:Lung / Q000821:virology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012141:Respiratory Tract Infections / Q000188:drug therapy / Q000503:physiopathology* / Q000821:virology; D018108:Respirovirus / Q000302:isolation & purification; D010253:Respirovirus Infections / Q000188:drug therapy / Q000503:physiopathology*; D013997:Time Factors
D003907:Dexamethasone