Eotaxin expression after segmental allergen challenge in subjects with atopic asthma

Expression of pulmonary eotaxin protein and mRNA was determined in six subj ects with atopic asthma and five nonatopic normal subjects. Levels of eotax in expression and eosinophil mobilization were compared before and after se gmental allergen challenge in subjects with atopic asthma. In the absence o f allergen challenge, we found significantly higher levels of eotaxin in th e bronchoalveolar lavage (BAL) fluid of subjects with asthma than in that o f normal subjects (25 +/- 3 versus 15 +/- 2 pg/ml, p < 0.05). BAL eotaxin l evels increased after segmental allergen challenge in all six subjects with atopic asthma tested, with a mean increase from 22 +/- 4 to 53 +/- 10 pg/m l (p = 0.013). Segmental allergen challenge was associated with a significa nt increase in the percentage of BAL macrophages and eosinophils that were immunopositive for eotaxin. Eotaxin mRNA was detectable by northern analysi s in BAL cells exclusively from allergen-challenged segments. Allergen-indu ced increases in eotaxin levels were strongly associated with increases in BAL eosinophil recovery (r(2) = 0.88, p = 0.0036). Segmental allergen chall enge also increased eotaxin expression in airway epithelial and endothelial cells obtained by endobronchial biopsy. These findings demonstrate, for th e first time, that the airways of subjects with allergic asthma respond to allergen by increasing eotaxin expression. The tissue loci of eotaxin expre ssion, the levels of eotaxin recovered in BAL fluid, and the association of eotaxin levels with eosinophil mobilization suggest either that eotaxin pl ays a mechanistic role in allergen-induced airway eosinophilia or that it s erves as a biomarker for the causal mechanisms.