Differential effect of glucocorticoids on pulmonary responses and eosinophils

The persistent airway hyperresponsiveness of Basenji-Greyhound (BG) dogs to 10% citric acid (CA) is abolished by chronic administration of methylprednisolone (MP) and is accompanied by the disappearance of eosinophils from the bronchoalveolar lavage (BAL) fluid. To determine whether the disappearance of eosinophils from BAL fluid was temporally related to the loss of airway responsiveness to CA, we investigated the time course of the reduction in airway responsiveness to CA and correlated it with changes in cell profiles in BAL fluid in a group of BG dogs treated with MP for 1 to 7 days. Six dogs in separate studies were pretreated with MP (2 mg/kg/day) subcutaneously for either 1, 3 or 7 days. Each dog served as its own control for each set of studies. Under thiopental anesthesia, lung resistance (RL) was calculated from transpulmonary pressure and flow measurements prior to and 5 minutes following the completion of a 10% CA aerosol. BAL was performed on a separate occasion with the animals pretreated with MP for either 1, 7, 10 or 14 days. Baseline RL was not significantly different in each control and treatment group. The pulmonary response to CA challenge was diminished following 1, 3 and 7 days of MP pretreatment. Although eosinophils disappeared from the peripheral blood following 1 day of MP treatment, eosinophils in BAL did not begin decreasing until 10 days of MP pretreatment. This temporal dissociation between CA hyperresponsiveness and eosinophils in the BAL fluid suggests that epithelial damage by toxic products of eosinophils in the airway lumen does not play a direct role in citric acid induced airway hyperresponsiveness in BG dogs.