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Asthma in NHP

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 allergen- specific 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 pathway 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.

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

Case Study: HDM - Induced Asthma in Cynomolgus Monkeys

Animal:   Two Cynomolgus monkeys, male, 6-8 kg, were enrolled.

Aim:  Pilot study to establish House dust mite (HDM)-induced asthma in Cynomolgus monkeys

Methods: Animals were sensitized with HDM in Alum saline suspension as schedule (a). Four weeks after last sensitization, monkeys were challenged as schedule (b).

Experimental Design

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Endpoint: Cell Differentiation Percentage in BALF

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