Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model.

TLDR

Airway inflammation is central to asthma, yet the specific contributions of individual inflammatory cells and mediators to airway hyperreactivity and lung morphology during allergic pulmonary inflammation remain unclear. The study aimed to determine the essential role of IL‑5 and eosinophils in initiating aeroallergen‑induced lung damage and airway hyperreactivity using IL‑5‑deficient mice. Mice were sensitized and challenged with ovalbumin, producing airway eosinophilia, extensive lung damage, and hyperreactivity to beta‑methacholine, mirroring asthma. IL‑5‑deficient mice lacked eosinophilia, lung damage, and airway hyperreactivity after aeroallergen challenge, and reconstitution of IL‑5 restored these responses, confirming IL‑5 and eosinophils as central mediators of allergic lung disease.

Abstract

Airways inflammation is thought to play a central role in the pathogenesis of asthma. However, the precise role that individual inflammatory cells and mediators play in the development of airways hyperreactivity and the morphological changes of the lung during allergic pulmonary inflammation is unknown. In this investigation we have used a mouse model of allergic pulmonary inflammation and interleukin (IL) 5-deficient mice to establish the essential role of this cytokine and eosinophils in the initiation of aeroallergen-induced lung damage and the development of airways hyperreactivity. Sensitization and aerosol challenge of mice with ovalbumin results in airways eosinophilia and extensive lung damage analogous to that seen in asthma. Aeroallergen-challenged mice also display airways hyperreactivity to beta-methacholine. In IL-5-deficient mice, the eosinophilia, lung damage, and airways hyperreactivity normally resulting from aeroallergen challenge were abolished. Reconstitution of IL-5 production with recombinant vaccinia viruses engineered to express this factor completely restored aeroallergen-induced eosinophilia and airways dysfunction. These results indicate that IL-5 and eosinophils are central mediators in the pathogenesis of allergic lung disease.