INTERLEUKIN-5 AND EOSINOPHILS INDUCE AIRWAY DAMAGE AND BRONCHIAL HYPERREACTIVITY DURING ALLERGIC AIRWAY INFLAMMATION IN BALB C MICE/

The cytokines IL-4 and IL-5 secreted from antigen-activated CD4(+) T c ells are thought to play central roles in the clinical expression and pathogenesis of asthma. However, there is conflicting evidence in anim al models of allergic airway inflammation as to the relative importanc e of IL-5 and eosinophils to the mechanisms underlying the induction o f bronchial hyperreactivity and morphological changes to the airways i n response to aeroallergen. In a recent investigation, the development of aeroallergen-induced bronchial hyperreactivity in BALB/c mice was thought to be exclusively regulated by IL-4, with no role for IL-5 or eosinophils being demonstrated. In contrast, allergic airway disease c ould not be induced in IL-5-deficient mice of the C57BL/6 strain. A mo del of allergic airway inflammation, which displays certain phenotypic characteristics of late-phase asthmatic responses, was used in the pr esent investigation to establish a role for IL-5 and eosinophils in th e initiation of bronchial hyperreactivity and in the pathogenesis of a llergic airway disease in BALB/c mice. Sensitization and repetitive ae rosolization of mice with ovalbumin resulted in a severe airway inflam matory response which directly correlated with the induction of extens ive airway damage and bronchial hyperreactivity to beta-methacholine. Treatment of mice with anti-IL-5 mAb before aeroallergen challenge, ab olished blood and airway eosinophilia, lung damage and significantly r educed bronchial hyperreactivity. These results show that IL-5 and eos inophilic inflammation play a substantial role in the pathophysiology of allergic airway disease and, moreover, that aeroallergen-induced br onchial hyperreactivity is not exclusively related by IL-4. These resu lts also suggest that eosinophils are predominantly responsible for re gulating aeroallergen-induced structural changes to the airways which contribute, in part, to the mechanism underlying the induction of bron chial hyperreactivity. Thus, there are at least two distinct pathophys iological mechanisms for the induction of aeroallergen-induced airway occlusion.