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 cells are thought to play central roles in the clinical expression and pathogenesis of asthma. However, there is conflicting evidence in animal models of allergic airway inflammation as to the relative importance of IL-5 and eosinophils to the mechanisms underlying the induction of bronchial hyperreactivity and morphological changes to the airways in 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 could not be induced in IL-5-deficient mice of the C57BL/6 strain. A model of allergic airway inflammation, which displays certain phenotypic characteristics of late-phase asthmatic responses, was used in the present investigation to establish a role for IL-5 and eosinophils in the initiation of bronchial hyperreactivity and in the pathogenesis of allergic airway disease in BALB/c mice. Sensitization and repetitive aerosolization of mice with ovalbumin resulted in a severe airway inflammatory response which directly correlated with the induction of extensive airway damage and bronchial hyperreactivity to beta-methacholine. Treatment of mice with anti-IL-5 mAb before aeroallergen challenge, abolished blood and airway eosinophilia, lung damage and significantly reduced bronchial hyperreactivity. These results show that IL-5 and eosinophilic inflammation play a substantial role in the pathophysiology of allergic airway disease and, moreover, that aeroallergen-induced bronchial hyperreactivity is not exclusively regulated by IL-4. These results also suggest that eosinophils are predominantly responsible for regulating aeroallergen-induced structural changes to the airways which contribute, in part, to the mechanism underlying the induction of bronchial hyperreactivity. Thus, there are at least two distinct pathophysiological mechanisms for the induction of aeroallergen-induced airway occlusion.
Hogan
S P
SP
Cellular Signal Transduction Laboratory, John Curtin School of Medical Research, Australian National University, Canberra, Australia.
Koskinen
A
A
Foster
P S
PS
D000485:Allergens / Q000008:administration & dosage; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001249:Asthma / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D004804:Eosinophils / Q000276:immunology*; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000502:physiology; D015848:Interleukin-5 / Q000037:antagonists & inhibitors / Q000502:physiology*; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology
D000485:Allergens; D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D015848:Interleukin-5; D015847:Interleukin-4; D010047:Ovalbumin