Prevention and reversal of pulmonary inflammation and airway hyperresponsiveness by dexamethasone treatment in a murine model of asthma induced by house dust.
The morbidity and mortality from asthma in the Western world have increased 75% in the past 20 years. Recent studies have demonstrated that sensitization to cockroach allergens correlates strongly with the increased asthma morbidity for adults and children. We investigated whether dexamethasone administered before or after allergen challenge would inhibit the pulmonary inflammation and airway hyperresponsiveness in a mouse model of asthma induced by a house dust extract with high levels of cockroach allergens. For the prevention experiment, mice were treated with an intraperitoneal injection of dexamethasone 1 h before each pulmonary challenge, and airway hyperresponsiveness was measured 24 h after the last challenge. Mice were killed 48 h after the last challenge. For the reversal study, airway hyperresponsiveness was measured 24 h after the last challenge, and the mice were treated with dexamethasone. Dexamethasone treatment before allergen challenge significantly reduced the pulmonary recruitment of inflammatory cells, myeloperoxidase activity in the lung, airway hyperreactivity, and total serum IgE levels compared with PBS-treated mice. Additionally, dexamethasone treatment could significantly reduce the airway hyperreactivity of an established asthmatic response. These results demonstrate that dexamethasone not only prevents but also halts the asthmatic response induced by house dust containing cockroach allergens. This model exhibits several features of human asthma that may be exploited in the study of pathophysiological mechanisms and potential therapeutic interventions.
Kim
Jiyoun
J
M2210 Med Sci I, 1301 Catherine Rd., Ann Arbor, MI 48109-0602, USA. jiyoukim@umich.edu
McKinley
Laura
L
Siddiqui
Javed
J
Bolgos
Gerry L
GL
Remick
Daniel G
DG
D000208:Acute Disease; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D004391:Dust / Q000276:immunology; D004804:Eosinophils / Q000276:immunology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D007073:Immunoglobulin E / Q000276:immunology; D016676:Macrophages, Alveolar / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000276:immunology; D011014:Pneumonia / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control
D004391:Dust; D005938:Glucocorticoids; D007073:Immunoglobulin E; D003907:Dexamethasone