To establish whether allergic
asthma could be induced experimentally in a nonhuman primate using a common human
allergen, three female rhesus monkeys (Macaca mulatta) were sensitized with house dust mite (Dermatophagoides farinae)
allergen (
HDMA) by
subcutaneous injection, followed by four intranasal sensitizations, and exposure to
allergen aerosol 3 hours per day, 3 days per week for up to 13 weeks. Before
aerosol challenge, all three monkeys skin-tested positive for
HDMA. During
aerosol challenge with
HDMA, sensitized monkeys exhibited
cough and rapid shallow breathing and increased airway resistance, which was reversed by
albuterol aerosol treatment. Compared to nonsensitized monkeys, there was a fourfold reduction in the dose of
histamine aerosol necessary to produce a 150% increase in airway resistance in sensitized monkeys. After
aerosol challenge, serum levels of
histamine were elevated in sensitized monkeys. Sensitized monkeys exhibited increased levels of
HDMA-specific
IgE in serum, numbers of eosinophils and exfoliated cells within lavage, and elevated CD25 expression on circulating CD4(+) lymphocytes. Intrapulmonary bronchi of sensitized monkeys had focal mucus cell
hyperplasia, interstitial infiltrates of eosinophils, and thickening of the basement membrane zone. We conclude that a model of allergic
asthma can be induced in rhesus monkeys using a protocol consisting of
subcutaneous injection, intranasal instillation, and
aerosol challenge with
HDMA.