House Dust Mite (HDM) induced acute allergic asthma in BALBc mice

Species

Mouse

Fields of application

Acute allergic asthma is induced by repeated intranasal administration of a whole dust mite extract. Besides impairment of lung function and distinct airway remodelling a number of immunological changes can be monitored for up to thirty days.

The model can be used for the following fields of application:

  • Pharmacodynamics and pharmacokinetics
  • (Patho)physiological processes
  • Therapeutic efficacy
  • Proof of concept

Endpoints / outcome parameter

  • Dynamic compliance, Lung resistance, Enhanced pause (lung function measurement; in vivo)
  • Immune cells in full blood (in vivo)
  • IgE titre and cytokine levels in blood plasma (in vivo)
  • Airway remodelling (upper airways and lung, including goblet cell hyperplasia, infiltration of eosinophils, fibrosis, airway narrowing; ex vivo)
  • BALF (bronchoalveolar lavage fluid) immune cell composition, cytokine levels, IgE titre (ex vivo)

Readout parameter

  • Invasive / non-invasive lung function measurements
  • Flow cytometry
  • ELISA / CBA (cytometric bead array)
  • RT-PCR
  • Western Blot
  • Histology / Cytology (various classical histological stains)
  • Immunohistochemistry

Quality management and validation

  • Controls
  • Blinded induction
  • Blinded data collection and analysis
  • Randomisation
  • Allocation concealment
  • Biometric Expertise
  • Internal quality management

References

Cooperation project with Nuvo Research GmbH (Leipzig): "Die Entwicklung des Wirkstoffes WF10 zu einer innovativen Arzneimittel-Plattform zur Therapie chronisch inflammatorischer Erkrankungen"

Flemmig J, Schwarz P, Bäcker I, Leichsenring A, Lange F, Arnhold J. Rapid and reliable determination of the halogenating peroxidase activity in blood samples. J Immunol Methods. 2014; 415:46-56

Airway remodelling in acute HDM induced allergic asthma in mice. A: Healthy lung tissue (HE stain). B: Fibrotic lung tissue of an allergic mouse. Besides fibrosis infiltration of eosinophils is clearly visible (arrows). C: Healthy lung tissue (PAS stain). D: Goblet cell hyperplasia and airway narrowing (arrows) in the lung of a mouse with acute HDM induced allergic asthma.
© Fraunhofer IZI
Airway remodelling in acute HDM induced allergic asthma in mice. A: Healthy lung tissue (HE stain). B: Fibrotic lung tissue of an allergic mouse. Besides fibrosis infiltration of eosinophils is clearly visible (arrows). C: Healthy lung tissue (PAS stain). D: Goblet cell hyperplasia and airway narrowing (arrows) in the lung of a mouse with acute HDM induced allergic asthma.