Technotes

Technotes

Asthma

Introduction



Asthma is a chronic inflammatory disorder of the airways in which many infiltrating cells (such as mast cells, eosinophils, T lymphocytes, macrophages, neutrophils, and epithelial cells) and cellular elements play critical roles. This inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness, and cough usually associated with widespread but variable airflow obstruction that is often reversible either spontaneously or with treatment. The inflammation also causes an associated increase in the existing bronchial hyper-responsiveness to a variety of stimuli, during which the high serum levels of immunoglobulin E (IgE) and intrapulmonary production of interleukin-4 (IL-4), IL-5, and IL-13 by allergenspecific Th2 cells become obvious. 


Airway inflammation is associated with the infiltration of eosinophils, neutrophils, and T and B lymphocytes into the airways and lung tissues. Understanding of the molecular pathogenesis of asthma has enabled the development of innovative agents to modulate specific components of the disease progress for early intervention or treatment. A number of experimentally induced asthma models have been used extensively as the mainstay for evaluation of those therapeutic agents and candidates.


PharmaLegacy Models and Research Tools




Pharmacology models and research tools:

* OVA induced asthma in BALB/c mice       

* OVA induced asthma in Brown-Norway rats


Model characteristics:

* Migration of inflammatory cells, in particular eosinophils and lymphocytes, into the lung tissue               

* Vasodilation and degranulation of mast cells

* Release of additional inflammatory mediators by Th2 lymphocytes, such as IL-4, IL-5 and IL-13, which play important roles in the pathogenesis of asthma         

* Destruction of epithelial layer

 

Measurement of pharmacology and inflammatory responses:

* Total cell numbers and differential cell counts in broncho-alveolar lavage fluid (BALF)

* Lung function test (airway hyper-responsiveness, Penh method)

* Serum levels of total and OVA-specific IgE

* IL-4, IL-5 and IL-13 levels in BALF and lung tissue (ELISA)

* IL-4 , IL-5 and IL-13 mRNA levels in lung tissue (qRT-PCR)       

* Histopathology analysis of infiltration


Case Study   -  OVA Induced Asthma in BALB/c Mice