The role of eosinophils as effector cells in asthma pathogenesis has been 
questioned since an anti-interleukin (IL)-5 monoclonal antibody (mepolizumab), 
which depleted blood and sputum eosinophils, failed to inhibit allergen-induced 
bronchoconstriction and airway hyperresponsiveness. However, the effect of IL-5 
blockade on tissue eosinophils was not examined. We sought to determine whether 
mepolizumab depletes airway tissue eosinophils and their products. Twenty-four 
patients with mild asthma received three intravenous doses of either 750 mg of 
mepolizumab or placebo in a randomized, double-blind, parallel-group fashion 
over 20 weeks. Mepolizumab produced a median decrease from baseline of 55% for 
airway eosinophils (interquartile range, 29-89%; p = 0.009 versus placebo), 52% 
for bone marrow eosinophils (45-76%, p = 0.003), and 100% for blood eosinophils 
(range, 67-100%, p = 0.02). Mepolizumab had no appreciable effect on bronchial 
mucosal staining of eosinophil major basic protein. There were no significant 
changes in clinical measures of asthma (airway hyperresponsiveness, FEV1, and 
peak flow recordings) between the mepolizumab and placebo-treated groups. 
Anti-IL-5 treatment reduces but does not deplete airway or bone marrow 
eosinophils. The role of the eosinophil remains uncertain. Further clinical 
studies in asthma with more effective antieosinophil strategies are required.