Premium
Effects of dexamethasone on airway hyper‐responsiveness to the adenosine A 1 receptor agonist cyclo‐pentyl adenosine in an allergic rabbit model
Author(s) -
ElHashim Ahmed Z,
Banner Katharine H,
Paul William,
Page Clive P
Publication year - 1999
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702455
Subject(s) - dexamethasone , medicine , bronchoalveolar lavage , endocrinology , methacholine , adenosine , agonist , immunology , receptor , lung , respiratory disease
New Zealand White (NZW) rabbits were immunized within 24 h of birth with Alternaria tenuis in aluminium hydroxide (Al (OH) 3 ) (i.p.) or sham immunized (saline plus Al (OH) 3 i.p.) and subsequently injected with the allergen (i.p.) or sham‐immunized for the next 3 months. At 3 months of age, baseline airway responsiveness was assessed using cyclo‐pentyl adenosine (CPA). Bronchoalveolar lavage (BAL) was performed in all animals and samples of peripheral blood were collected from some animals for estimation of dexamethasone levels. In some animals, blood was collected at the end of the experiment and cellular function was assessed by measurement of ex vivo proliferation of mononuclear cells in response to phytohaemagglutinin (PHA). Allergen immunization significantly increased baseline airway responsiveness to inhaled CPA ( P <0.05) in comparison with sham‐immunized animals, at 3 months after immunization. Dexamethasone (0.5 mg kg −1 day −1 ) treatment for 1 month did not modify this established airway hyper‐responsiveness to CPA. Dexamethasone treatment did not affect either total or differential cell numbers in BAL fluid during the 4 week period, although significant plasma levels of dexamethasone were achieved in dexamethasone treated animals. Treatment of rabbits with dexamethasone (0.1 mg kg −1 i.p.), 6 h prior to each allergen injection from the neonatal stage, significantly reduced baseline airway hyper‐responsiveness to CPA measured at 3 months ( P <0.05). There was no significant difference in either total or differential cell numbers in BAL fluid, or any difference in mitogen‐induced proliferation of mononuclear cells between dexamethasone and vehicle treated rabbits. These results suggest that introduction of glucocorticosteroids in early life can prevent baseline airway hyper‐responsiveness to inhaled CPA in allergic rabbits. However, once established, such underlying airway hyper‐responsiveness is difficult to resolve, even with prolonged treatment with glucocorticosteroids.British Journal of Pharmacology (1999) 126 , 1513–1521; doi: 10.1038/sj.bjp.0702455