Interleukin (IL)-5 but Not Immunoglobulin E Reconstitutes Airway Inflammation and Airway Hyperresponsiveness in IL-4–Deficient Mice

Eckard Hamelmann, Katsuyuki Takeda, Angela Haczku, Grzegorz Cieslewicz, Leonard Shultz, Qutayba Hamid, Zhou Xing, Jack Gauldie, Erwin W. Gelfand
2000 American Journal of Respiratory Cell and Molecular Biology  
We studied the role of interleukin (IL)-4, IL-5, and allergenspecific immunoglobulin (Ig) E in the development of allergen-induced sensitization, airway 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 sensitization and airway challenge, normal and IL-5-deficient, but not IL-4-deficient, mice developed increased serum levels of
more » ... sed serum levels of total and antigen-specific IgE levels and increased IL-4 production in the lung tissue compared with nonsensitized control mice. Only normal mice showed significantly increased IL-5 production in the lung tissue and an eosinophilic infiltration of the peribronchial regions of the airways, whereas both IL-4-and IL-5-deficient mice had little or no IL-5 production and no significant eosinophilic airway 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 mice. Reconstitution of sensitized, IL-4-deficient mice before allergen airway challenge with IL-5, but not with allergen-specific IgE, restored eosinophilic airway inflammation and the development of AHR. These data demonstrate the importance of IL-4 for allergen-driven airway sensitization and that IL-5, but not allergen-specific IgE, is required for development of eosinophilic airway inflammation and AHR after this mode of sensitization and challenge.
doi:10.1165/ajrcmb.23.3.3796 pmid:10970823 fatcat:i4o7xa5wjjh45p4toi5xujgfhy