Relationships among numbers of bronchoalveolar lavage cells expressing messenger ribonucleic acid for cytokines, asthma symptoms, and airway methacholine responsiveness in atopic asthma

Abstract

Background: We recently demonstrated that T lymphocytes in bronchoalveolar lavage (BAL) fluid from atopic asthmatic patients were activated and expressed increased cytokine messenger ribonucleic acid (mRNA) for “T H2-type” cytokines, particularly IL-4 and IL-5, when compared with those in normal control subjects. This pattern of cytokines may determine the nature of the cellular infiltrate in the bronchial mucosa in asthma and hence the bronchial hyperresponsiveness (BHR) and symptoms that characterize this condition. Methods: To examine the association between these cytokines and clinical measures of asthma severity we have extended our studies of BAL cells from subjects with atopic asthma. Numbers of BAL cells with positive in situ hybridization signals for IL-2, IL-3, IL-4, IL-5, granulocyte macrophage colony-stimulating factor (GM-CSF), and Interferon-γ were counted on cytocentrifuge preparations. Results were compared between patients with symptomatic ( n = 19) and asymptomatic asthma ( n = 10), and associations were sought with airway methacholine responsiveness, resting airway caliber, and asthma symptom scores. Results: There were increased proportions of cells positive for IL-3 ( p < 0.05), IL-4 ( p < 0.005), IL-5 ( p < 0.005), and GM-CSF ( p < 0.005) mRNA in BAL fluid from patients with symptomatic asthma when compared with that from subjects free of symptoms, but no difference between the groups in numbers of cells expressing IL-2 and interferon-γ mRNA. There were significant associations among numbers of cells expressing mRNA for IL-4, IL-5, and GM-CSF, and airflow restriction, BHR, and Aas asthma score. Conclusions: These findings support the hypothesis that cytokines contribute to airway events that determine asthma symptoms and BHR.