Murine asthma models.

Immunotoxicity can take the form of an enhanced immune response or hypersensitivity. Asthma is one possible consequence of hypersensitivity in the lung, with characteristics that include reversible airway obstruction, eosinophil infiltration into the lung, and airway hyperresponsiveness to agonists such as methacholine. In toxicology, two primary areas of investigation prompt the measurement of the asthmatic response in an animal: (1) identification of chemicals or proteins that cause asthma, i.e., respiratory allergens, and (2) identification of exposures that will exacerbate existing asthma. An ovalbumin-induced asthma model can be used to identify exposures that exacerbate existing asthma. A protocol for the sensitization and challenge of mice with ovalbumin is described; it leads to the asthma symptoms of airway hyperresponsiveness and eosinophil infiltration. Assessment of airway hyperresponsiveness to methacholine uses whole body plethysmography in conscious unrestrained mice. Bronchoalveolar lavage of the mouse determines the extent of cellular infiltration into the airspace. Removal of lung lobes and assay of eosinophil peroxidase and myeloperoxidase provides a measure of the numbers of eosinophils and neutrophils, respectively, in the lung. Depending on the experimental goals, bronchoalveolar lavage fluid and lung tissue can also be used for isolation of RNA, and measurement of cytokines, chemokines, antibodies, and inflammatory mediators.