Inhibition of airway remodeling in IL-5–deficient mice

Abstract

Ab's have shown inhibition of allergen-induced airway responsiveness, however (8).Transgenic mice that have been molecularly engineered to constitutively express IL-5 in the lung epithelium develop accumulation of peribronchial eosinophils, goblet cell hyperplasia, epithelial hypertrophy, focal collagen deposition, and airway hyperresponsiveness to methacholine in the absence of aerosolized antigen challenge (5).Moreover, adoptive transfer of eosinophils directly into the lungs of OVA-challenged IL-5-deficient mice results in restoration of pulmonary eosinophilia equivalent to that observed in OVA-challenged WT mice, as well as restoration of the development of airway hyperresponsiveness (9).Recent studies suggest that inhibition of both IL-5 and the eosinophil chemoattractant eotaxin results in more complete inhibition of acute allergeninduced eosinophilic inflammation than targeting either IL-5 or eotaxin alone (10).Thus, in the mouse there is considerable evidence that IL-5 plays a prominent role in the development of acute allergen-induced airway eosinophilia, as well as airway responsiveness in most, but not all studies.In humans with asthma there is also evidence that IL-5 may play a role in the pathogenesis of eosinophilic inflammation and asthma.Airway allergen challenge in asthmatics induces expression of IL-5 by T lymphocytes (11) and eosinophils (12), while increased levels of IL-5 and eosinophil granule proteins can be detected in the airway of symptomatic asthmatics (13).Inhalation of IL-5 induces airway eosinophilia and airway hyperreactivity to methacholine in human asthmatics ( 14).Initial studies with anti-IL-5 in mild asthmatics demonstrated that anti-IL-5 was effective in inhibiting eosinophils from the bone marrow to the lung is IL-5, which regulates eosinophil proliferation, differentiation, and release from the bone marrow (1-3).In vivo studies performed in either IL-5-deficient mice (4), IL-5-transgenic mice (5), or mice treated with anti-IL-5 Ab's (6) have suggested an important role for IL-5 in acute allergen-induced eosinophilic inflammation and airway hyperreactivity.In IL-5-deficient mice there is a significant reduction in the level of bronchoalveolar eosinophila following OVA allergen challenge, which is associated with significantly less airway hyperreactivity to methacholine (4).Similarly, mice treated with an anti-IL-5 Ab prior to allergen challenge have significantly less airway eosinophilia and airway responsiveness (6, 7).Not all studies in mice treated with anti-IL-5