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2622340 
Journal Article 
Abstract 
Development of a murine model of lung inflammation and airway hyperresponsiveness driven by house dust mite in complete freund's adjuvant 
Nasra, J; Tomlinson, KL; Catley, M; Palframan, R; Watt, G; Shaw, S; Gozzard, N 
2010 
Yes 
American Journal of Respiratory and Critical Care Medicine
ISSN: 1073-449X
EISSN: 1535-4970 
181 
A2842 
English 
WOS:000208771001754 
is part of a larger document 3452678 Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans
RATIONALE: The aim was to develop an allergen-induced murine model of airway inflammation, characterised by airway hyperresponsiveness (AHR) and an upregulation of Th1 and Th2 cytokines.

METHODS: C57BL/6 or BALB/c mice (male, 20-25g) were sensitised subcutaneously on day 0 with vehicle or 100µg of house dust mite (Dermatophagoides pteronyssinus (Der p)) extract in complete Freund’s adjuvant. On day 14, mice were exposed to saline or Der p (0.25/ 2.5/ 25/ 100µg) via intranasal instillation. 48 hours post-challenge, non-invasive whole-body plethysmography was used to assess AHR stimulated by aerosolised methacholine (MCh, 3.125-50mg/ml). Bronchoalveolar lavage fluid (BALF) was retrieved for measurement of inflammatory cells and cytokine profile. Blood serum was retrieved for analysis of house dust mite specific antibodies.

RESULTS: Allergen-induced AHR was more profound in BALB/c compared to C57BL/6 mice. Sensitisation and challenge of BALB/c mice with Der p induced AHR (>2-fold increase in Penh at all concentrations of MCh), whereas AHR in C57BL/6 mice was less robust (>2-fold increase only at 6.25 and 12.5mg/ml MCh). The AHR was accompanied by BALF neutrophilia (BALB/c: 83.66±17.31 x10^4 cells/ml; C57BL/6: 47.10±21.62 x10^4 cells/ml) and eosinophilia (BALB/c: 17.51±5.07 x10^4 cells/ml; C57BL/6: 11.43±5.58 x10^4 cells/ml). In subsequent studies using BALB/c mice, 25µg was selected as the optimal Der p challenge dose. Further characterisation shows that sensitisation and challenge with Der p induces a significant (p<0.05) upregulation of Th1 and Th2 cytokines in the BALF (IFNγ, IL-12, IL-4, IL-5, IL-1b, IL-2, KC and TNFα) and of IgE, IgG1, IgG2a and IgG2b in the serum.

CONCLUSIONS: The distinction in the responses between BALB/c and C57BL/6 mice following Der p sensitisation and challenge highlights that it is important to consider the strain when designing new murine models. This model mimics certain aspects of persistent asthma and will be used to investigate mechanisms underlying this disease and in the assessment of novel therapeutics. 
American Thoracic Society 2010 International Conference 
New Orleans, LA 
May 14-19, 2010