Cessation of dexamethasone exacerbates airway responses to methacholine in asthmatic mice.
In asthmatic mice, dexamethasone (30.0 mg/kg) was administered orally once daily on Days 24-27. One hour after dexamethasone on Day 25-27, the mice were exposed to ovalbumin aerosols. Twenty-eight days after the initial ovalbumin immunization, we found that dexamethasone reduced methacholine-induced pulmonary gas trapping and inhibited bronchoalveolar lavage eosinophils and neutrophils. However, five days after the last dose of dexamethasone and last ovalbumin aerosol exposure in other asthmatic mice, the airway obstructive response to methacholine was exacerbated in dexamethasone-treated mice compared to vehicle-treated mice on Day 32. Further, eosinophils, but not neutrophils, were still inhibited after cessation of dexamethasone. Thus, discontinuing dexamethasone worsened methacholine-induced pulmonary gas trapping of asthmatic mice in the absence of eosinophilic airway inflammation.
Stengel
Peter W
PW
Eli Lilly and Company, Lilly Research Laboratories, 2001 West Main Street, Greenfield, Indiana 46140, USA. stengel_peter_w@lilly.com
Nickell
Laura E
LE
Wolos
Jeffrey A
JA
Snyder
David W
DW
D000284:Administration, Oral; D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000503:physiopathology* / Q000517:prevention & control; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016085:Bronchoconstrictor Agents / Q000494:pharmacology*; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004804:Eosinophils / Q000187:drug effects; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000187:drug effects; D010047:Ovalbumin; D011657:Pulmonary Eosinophilia / Q000503:physiopathology / Q000517:prevention & control; D012008:Recurrence
D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride; D003907:Dexamethasone; D010047:Ovalbumin