PREDNISOLONE TREATMENT IN ASTHMA IS ASSOCIATED WITH MODULATION OF BRONCHOALVEOLAR LAVAGE CELL INTERLEUKIN-4, INTERLEUKIN-5, AND INTERFERON-GAMMA CYTOKINE GENE-EXPRESSION

Although corticosteroids are effective in improving asthma symptoms an d bronchial responsiveness, their mechanism of action is unknown. We e xamined whether changes in bronchial responsiveness with corticosteroi d therapy of asthma are accompanied by a reduction in cytokine gene ex pression and eosinophil infiltration in the airways. Bronchoalveolar l avage (BAL) was performed in 18 patients with moderate asthma before a nd after 2 wk of treatment with prednisolone, 0.6 mg/kg/day, or matche d placebo in a randomized double-blind parallel group study. Cells wer e counted in BAL cytocentrifuge preparations, and the numbers of cells expressing cytokine mRNA were assessed by in situ hybridization using S-35-labeled RNA probes. When the actively treated and placebo groups were compared, there was a decrease in airway methacholine responsive ness (p < 0.01) after prednisolone. This was accompanied by a decrease in bronchoalveolar lavage eosinophils (p < 0.05), a reduction in the numbers of BAL cells per 1,000 expressing mRNA for interleukin-4 (IL-4 , p < 0.01) and interleukin-5 (IL-5, p < 0.005), and an increase in nu mbers of cells expressing mRNA for interferon-gamma (p < 0.005). These results are compatible with the hypothesis that the beneficial effect s of corticosteroids in asthma may result from modulation of cytokine production, with consequent inhibition of local bronchial eosinophilia .