The trials and tribulations of IL-5, eosinophils, and allergic asthma☆

Abstract 

Eosinophils have been suggested to be part of the pathologic process that characterizes asthma, and their recruitment into the upper or lower airways appears to be essential for the clinical manifestations of allergen inhalation. IL-5 is a cytokine necessary for the development, differentiation, recruitment, activation, and survival of eosinophils. Allergen inhalation increases the production of IL-5 in the airways as measured in bronchoalveolar lavage cells and induced sputum. The relationship between IL-5 and the development of airway eosinophilia has been firmly established in IL-5 transgenic mice, with allergen challenge models in IL-5–deficient mice, and in mice treated with blocking anti–IL-5 antibodies. In addition, an accumulation of evidence suggests that treating mice with anti–IL-5 blocking antibodies prevents allergen-induced airway hyperresponsiveness. A recently reported study examined the effects of treatment with a humanized anti–IL-5 mAb (SB-240563) on allergen-induced airway responses and inflammation in atopic subjects. The authors of the study concluded that their results call into question the role of eosinophils in mediating the allergen-induced late asthmatic response and airway hyperresponsiveness; however, because of methodologic limitations, the study cannot be used either to support or to refute the concept of an important role for eosinophils in causing allergen-induced changes in airway function. (J Allergy Clin Immunol 2001;108:503-8.)

Keywords:  Interleukin-5, eosinophils, allergen, asthma, airway hyperresponsiveness, late asthmatic responses

Abbreviations:  AHR: , Airway hyperresponsiveness, Eo/B-CFU: , Eosinophil/basophil colony-forming unit, hmAb: , Humanized monoclonal antibody, IL-5KO: , IL-5–deficient, IL-4KO: , IL-4–deficient, PC₂₀: , Provocative concentration causing a 20% fall in FEV₁