Interleukin (IL)-5 but not immunoglobulin E reconstitutes airway inflammation and airway hyperresponsiveness in IL-4-deficient mice

We studied the role of interleukin (IL)-4, IL-5, and allergen-specific immu noglobulin (Ig) E in the development of allergen-induced sensitization, air way inflammation, and airway hyperresponsiveness (AHR). Normal, IL-4-, and IL-5-deficient C57BL/6 mice were sensitized intraperitoneally to ovalbumin (OVA) and repeatedly challenged with OVA via the airways. After allergen se nsitization and airway challenge, normal and IL-5-deficient, but not IL-4-d eficient, mice developed increased serum levels of total and antigen-specif ic IgE levels and increased IL-4 production in the lung tissue compared wit h nonsensitized control mice. Only normal mice showed significantly increas ed IL-5 production in the lung tissue and an eosinophilic infiltration of t he peribronchial regions of the airways, whereas both IL-4- and IL-5-defici ent mice had little or no IL-5 production and no significant eosinophilic a irway inflammation. Associated with the inflammatory responses in the lung, only normal mice developed increased airway responsiveness to methacholine after sensitization and airway challenge; in both IL-4- and IL-5-deficient mice, airway responsiveness was similar to that in nonsensitized control m ice. Reconstitution of sensitized, IL-4-deficient mice before allergen airw ay challenge with IL-5, but not with allergen-specific IgE, restored eosino philic airway inflammation and the development of AHR. These data demonstra te the importance of IL-4 for allergen-driven airway sensitization and that IL-5, but not allergen-specific IgE, is required for development of eosino philic airway inflammation and AHR after this mode of sensitization and cha llenge.