Article

Prolonged allergen challenge in mice leads to persistent airway remodelling.

Leukocyte Biology Section, Division of Biomedical Sciences, Faculty of Medicine, Imperial College, London, UK.
Clinical & Experimental Allergy (impact factor: 5.03). 04/2004; 34(3):497-507.
Source: PubMed

ABSTRACT Inflammatory infiltrates, airway hyper-responsiveness, goblet cell hyperplasia and subepithelial thickening are characteristic of chronic asthma. Current animal models of allergen-induced airway inflammation generally concentrate on the acute inflammation following allergen exposure and fail to mimic all of these features.
The aim of this study was to use a murine model of prolonged allergen-induced airway inflammation in order to characterize the cells and molecules involved in the ensuing airway remodelling. Moreover, we investigated whether remodelling persists in the absence of continued allergen challenge.
Acute pulmonary eosinophilia and airways hyper-reactivity were induced after six serial allergen challenges in sensitized mice (acute phase). Mice were subsequently challenged three times a week with ovalbumin (OVA) (chronic phase) up to day 55. To investigate the persistence of pathology, one group of mice were left for another 4 weeks without further allergen challenge (day 80).
The extended OVA challenge protocol caused significant airway remodelling, which was absent in the acute phase. Specifically, remodelling was characterized by deposition of collagen as well as airway smooth muscle and goblet cell hyperplasia. Importantly, these airway changes, together with tissue eosinophilia were sustained in the absence of further allergen challenge. Examination of cytokines revealed a dramatic up-regulation of IL-4 and tumour growth factor-beta1 during the chronic phase. Interestingly, while IL-4 levels were significantly increased during the chronic phase, levels of IL-13 fell. Levels of the Th1-associated cytokine IFN-gamma also increased during the chronic phase.
In conclusion, we have demonstrated that prolonged allergen challenge results in persistent airway wall remodelling.

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Keywords

acute phase
 
Acute pulmonary eosinophilia
 
airway hyper-responsiveness
 
airway smooth muscle
 
airways hyper-reactivity
 
allergen-induced airway inflammation
 
chronic asthma
 
chronic phase
 
Current animal models
 
cytokines
 
ensuing airway remodelling
 
goblet cell hyperplasia
 
IL-4 levels
 
murine model
 
persistent airway wall remodelling
 
prolonged allergen challenge results
 
serial allergen challenges
 
significant airway remodelling
 
Th1-associated cytokine IFN-gamma
 
tumour growth factor-beta1