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Dust mite-induced asthma in cynomolgus monkeys

Departments of ¹Physiology, ²Medicine, and ³Comparative Medicine, East Carolina University, Greenville, North Carolina 27858; ⁴LABS of Virginia^c, Yemassee, South Carolina 29945; and ⁵EpiGenesis Pharmaceuticals, Cranbury, New Jersey 08520

Submitted 17 October 2003 ; accepted in final form 5 December 2003

Animal models exhibiting high homology with humans at the genetic and pathophysiological levels will facilitate identification and validation of gene targets underlying asthma. In the present study, a nonhuman primate model of allergic asthma was developed by sensitizing cynomolgus monkeys to dust mite antigen. Sensitization elevated allergen-specific serum IgE and IgG levels, and peripheral blood mononuclear cells isolated from sensitized animals released IL-4, IL-5, and IL-10, but not IFN-. Aerosolized allergen decreased dynamic compliance and induced airway inflammation and hyperresponsiveness to aerosolized histamine. Albuterol and dexamethasone inhibited the airway constriction and allergen-induced inflammation, respectively. Airway wall remodeling that included goblet cell hyperplasia, basement membrane thickening, and smooth muscle hypertrophy was particularly evident in neonatally sensitized animals. In contrast to animals sensitized as adults, neonatally sensitized animals exhibited increased sensitivity to adenosine and larger allergen-induced changes in airway resistance and dynamic compliance. These results demonstrate that sensitization of cynomolgus monkeys with dust mite induces asthmalike symptoms, some of which may be dependent on age at the time of sensitization.

airway hyperresponsiveness; airway remodeling; cytokines; histamine; adenosine; compliance; resistance

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