Reversibility of airway inflammation and remodelling following cessation of antigenic challenge in a model of chronic asthma.
BACKGROUND
Asthma is associated with recruitment of eosinophils, accumulation of chronic inflammatory cells in the airway walls, subepithelial fibrosis and other structural changes of airway wall remodelling. The role of ongoing exposure to allergens in their pathogenesis remains unclear.


OBJECTIVE
To examine whether changes of inflammation and remodelling were reversible following cessation of antigenic challenge in a mouse model of chronic asthma.


METHODS
BALB/c mice sensitized to ovalbumin (OVA) were chronically challenged by inhalation of a low mass concentration of antigen for 8 weeks, leading to development of acute-on-chronic airway inflammation, subepithelial fibrosis and other changes of airway wall remodelling. Epithelial injury was assessed by immunohistochemistry, while inflammation and remodelling were quantified by appropriate histomorphometric techniques. Regression of lesions was assessed in animals examined at 1, 2 and 4 weeks after exposure to OVA ceased.


RESULTS
We did not find evidence of airway epithelial injury in this model of low-level chronic inhalational exposure to antigen. Persistence of the recruitment of eosinophils and chronic inflammatory cells in the airway walls was dependent on continuing antigenic challenge, as was persistence of mucous cell hyperplasia/metaplasia. Subepithelial fibrosis and epithelial hypertrophy exhibited delayed reversibility following cessation of exposure to antigen, possibly related to matrix-associated accumulation of transforming growth factor-beta(1).


CONCLUSIONS
In chronic asthma, low-level antigenic challenge may be required to maintain the inflammatory response in the airway wall, but airway remodelling may persist in its absence.
Kumar
R K
RK
Department of Pathology, University of New South Wales, Sydney, Australia. R.Kumar@unsw.edu.au
Herbert
C
C
Kasper
M
M
D000280:Administration, Inhalation; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002908:Chronic Disease; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D005355:Fibrosis / Q000276:immunology; D006965:Hyperplasia / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D012075:Remission, Spontaneous; D020545:Respiratory Mucosa / Q000378:metabolism / Q000473:pathology; D014132:Trachea / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1
D000485:Allergens; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D010047:Ovalbumin