Ovalbumin-induced acute asthma model in mice and rats

 

The Ova mouse model of acute allergic asthma is a well-established asthma model. Mice or Brown-Norway rats will be sensitized systemically and challenged inhalationally with ovalbumin. During the challenge the early airway response (EAR) and 4-5 h later the late airway response (LAR) can be registered by lung function measurement. After 24 h or 48 h, using a second lung function measurement, the airway hyperresponsiveness will be registered followed by a bronchoalveolar lavage with immunologic and histologic analyses of the inflammatory allergic response. Exact individual dosing during inhalation provocation or drug treatments will be achieved by means of a computerized feedback dose-control system.

Species

Mouse, rat

Fields of application

  • Preclinical efficacy testing

Endpoints/Outcome parameter

  • Early Airway Response (EAR)
  • Allergic Airway Inflammation & Airway Hyperresponsiveness (AHR)Tumor (patho)histology (ex vivo)

Readout parameter

  • Lung function measurements e.g. early airway response (EAR) and airway hyperresponsiveness (AHR)
  • Bronchoalveolar lavage: cell count + differential cell count (incl. inflammatory cells), cytokine profiles,
  • Cytokine profiles (ELISA, MSD)
  • Histology: conventional staining and tissue pathohistology/conventional microscopy (e.g. tissue cell infiltration), immunohistochemistry/fluorescence microscopy, confocal microscopy (e.g. for detection of targets e.g. receptor expression)
  • Lung tissue analysis (RNA isolation/ gene expression, cytokine profiles,…)
  • Flow cytometric analysis

Quality management and validation

  • Internal quality management
  • Historical data available
  • Reference compounds e.g. dexamethasone, fluticasone

Performance under GLP possible

References

  • Hoymann H.G. and Heinrich, U. Measurement of lung function in rodents in vivo. In: Methods in pulmonary research, edited by Uhlig, S. and Taylor, A.E., Birkhäuser Verlag, Basel, 1-28, 1998

  • Glaab T., and Hoymann Glaab T., and Hoymann H.G. contr. eq., Hohlfeld, J., Korolewitz, R., Hecht, M., Alarie, Y., Tschernig, T., Braun, A., Krug, N., and Fabel, H.: Noninvasive measurement of midexpiratory flow indicates bronchoconstriction in allergic rats, Journal of Applied Physiology 93:1208, 2002.

  • Glaab, T., Hoymann, H. G., Hecht, M., Korolewitz, R., Tschernig, T., Hohlfeld, J., Krug, N., and Braun, A.: Effect of anti-nerve growth factor on early and late airway responses in allergic rats. Allergy  58:900-904, 2003.

  • Duechs, M. J., Hahn, C., Benediktus, E., Werner-Klein, M., Braun, A., Hoymann, H. G., Gantner, F., Erb, K. J.: TLR agonist mediated suppression of allergic responses is associated with increased innate inflammation in the airways. Pulm.Pharmacol.Ther. 24:203-214, 2011.

  • Rückert, R., Brandt, K., Braun, A., Hoymann, H. G., Herz, U., Budagian, V., Dürkop, H., Renz, H., Bulfone-Paus, S.: Blocking IL-15 prevents the induction of allergen-specific T-cells and allergic inflammation in vivo. J Immunol.: 174(9):5507-5515, 2005.

  • Weigt, H. et al: Efficacy of Macrophage-activating Lipopeptide-2 Combined with Interferon-γ in a Murine Asthma Model. Am J Respir Crit Care Med Vol 172. pp 566–572, 2005

  • Hoymann, H. G.: Appraisal of state-of-the-art:  Invasive and Noninvasive Lung Function Measurements in Rodents. Journal of Pharmacological and Toxicological Methods 55(1):16-26, 2007.

  • Winkler, C., Bahlmann, O., Viereck, J., Knudsen, L., Wedekind, D., Hoymann, H. G., Madsen, J., Thum, T., Hohlfeld, J. M., Ochs, M.: Impact of a Met(11)Thr single nucleotide polymorphism of surfactant protein D on allergic airway inflammation in a murine asthma model. Exp.Lung Res. 40(4):154-163, 2014.