For over 20 years, we have speculated that eosinophils are the rapid improvement in FEV1 is difficult to interpret, and key effector cells in the pathogenesis of asthma (1). The dis- the fact that it was not sustained and only observed with the covery of interleukin (IL)-5, a cytokine that is essential for submaximal dose was disappointing. This finding may have terminal differentiation of the committed eosinophil precur- been related to the more acute bronchoconstricting effect sor (2), which also activates (3) and prolongs survival of the of eosinophil-derived cysteinyl leukotrienes or even to an mature cell in the tissues (4), offered an opportunity to test eosinophil-independent property as airway smooth muscle this eosinophil hypothesis. Leckie and coworkers, however, cells express the IL-5 receptor and in vitro incubation with surprisingly found that a monoclonal antibody directed IL-5 selectively primes for hyperresponsiveness (8). Thus, against IL-5 (mepolizumab) had no effect on either the late the rapid improvement in FEV1 may have been due to direct asthmatic reaction or airway hyperresponsiveness after infublockade of the actions of IL-5 on airway smooth muscle, sion in patients with mild atopic asthma (5). One explanation which in turn improved airway caliber. for these findings was that these patients’ asthma was too The eosinophil may have a role not only in acute/subacute mild to show an appreciable clinical effect of eosinophil processes involved in airway narrowing but in more downdepletion and that this form of treatment would only be stream events, such as repair and remodeling resulting from effective in subjects with more severe disease. chronic eosinophilic inflammation. In this regard, it is of inter-