IL-5 deficiency abolishes aspects of airway remodelling in a murine model of lung inflammation.
OBJECTIVE
Lung remodelling is a recognized feature of chronic asthma. In the present study, we have used IL-5-deficient mice to evaluate the role of this cytokine and eosinophilic inflammation in the initial stages of the structural changes occurring in the lung after antigen challenge.


METHODS
Ovalbumin-sensitized wild type and IL-5-deficient mice were daily challenged for 5 consecutive days and killed 3 or 7 days after the last challenge to study the inflammatory and remodelling events, respectively.


RESULTS
Wild type mice challenged with ovalbumin exhibited an accumulation of eosinophils in the bronchoalveolar lavage (BAL) fluid, associated with a production of BAL cellular fibronectin. Histological analysis also revealed an antigen-specific increase in epithelial and alveolar cell proliferation together with an increase in mucus producing epithelial cells. Eosinophilic infiltration and the associated lung remodelling were totally abrogated in IL-5-deficient mice. In wild type mice, treated intranasally with 1 microg of murine IL-5 for 5 consecutive days, no BAL eosinophilia and structural changes of the lungs could be observed.


CONCLUSIONS
Our results demonstrate that eosinophil accumulation, but not IL-5 alone, plays a central role in the initial stages of the lung remodelling process and suggests that therapies directed at inhibiting eosinophilic inflammation may be beneficial in treating chronic asthma.
Trifilieff
A
A
Novartis Horsham Research Centre, Horsham, UK. alexandre.trifilieff@pharma.novartis.com
Fujitani
Y
Y
Coyle
A J
AJ
Kopf
M
M
Bertrand
C
C
D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000276:immunology; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002908:Chronic Disease; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000139:chemically induced / Q000188:drug therapy; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology; D005260:Female; D007114:Immunization; D015848:Interleukin-5 / Q000172:deficiency* / Q000276:immunology / Q000627:therapeutic use*; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D010047:Ovalbumin / Q000494:pharmacology; D011014:Pneumonia / Q000276:immunology / Q000473:pathology*
D015848:Interleukin-5; D010047:Ovalbumin