Intranasal challenge with increasing ovalbumin doses differently affects airway hyperresponsiveness and inflammatory cell accumulation in mouse model of asthma
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To investigate whether challenge with increasing allergen doses could differently affect allergen-induced airway hyperresponsiveness (AHR) and inflammatory cell accumulation in mouse model of asthma, providing an experimental model to investigate their relationship.
Material and methods
AHR and accumulation of inflammatory cells in bronchoalveolar lavage fluid (BALF) and into the lungs were compared in ovalbumin-sensitized mice that were challenged intranasally with 2.5, 10, 25 or 100 μg of ovalbumin/mouse.
Both AHR and inflammatory cell accumulation were proportional to the ovalbumin dose used for challenge. However, in group challenged with 10 μg of ovalbumin airway inflammation was present, although allergen-induced AHR was not detected. Additional analysis indicated that neither mucous hyperproduction nor eosinophil degranulation could be correlated to presence of AHR in this model, whereas concentration of interleukin (IL)-13 in BALF was increased only in those groups in which AHR was present.
Altogether, intranasal challenge of mice with increasing allergen doses could serve as a suitable experimental system for investigation of mechanisms by which airway inflammation leads to allergen-induced AHR. Our initial findings are in line with previous reports that dissociate AHR from amount of eosinophil accumulation and imply the role of IL-13 in this process.
KeywordsAirway hyperresponsiveness Allergen dose Asthma Eosinophils Mice
Bronchoalveolar lavage fluid
Standard error of the mean
This work was supported by GlaxoSmithKline Research Centre Zagreb Limited, Zagreb, Croatia. The authors wish to acknowledge the excellent technical help of Ms M. Horvatinčić, I. Novaković, R. Povrženić, S. Skender, M. Škalic and Mr V. Vrban. The authors would also like to thank Drs Alenka Gagro and Michael J. Parnham for insightful comments during manuscript preparation.
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