EE is an emerging disease reported in children and adults of urbanized countries, where indoor insect
allergens are major health risk factors. Review of our hospital patient database uncovered that a number of EE patients have
hypersensitivity to indoor cat, dog, cockroach, and dust mite
allergens. We tested the hypothesis whether inhaled indoor insect
allergens are effective inducers of experimental EE. We delivered cat, dog, cockroach, and dust mite
allergen extracts intranasally to wild-type and
eotaxin-1/2-, CCR3-, and IL-5-deficient mice. Interestingly, wild-type mice exposed to cockroach or dust mite
allergens develop a significant increase in the levels of esophageal eosinophils and mast cells compared with saline-challenged mice. The eosinophil numbers in the esophagus of cockroach- and dust mite-exposed mice were 18.3+/-6.8/mm2 and 33.4+/-11.1/mm2 compared with 2.3+/-1.8/mm2 and 2.1+/-1.2/mm2 in saline-challenged mice. Additionally, we observed an additive effect of these two
allergens in inducing esophageal
eosinophilia and
mastocytosis. Histopathological analysis detected intraepithelial esophageal
eosinophilia in mice exposed to both
allergens. Furthermore, mice exposed to cockroach and/or dust mite had increased levels of total
IgE and
antigen-specific
IgG1 in the blood and increased esophageal expression of eosinophil-active
cytokines (IL-13) and
chemokines (eotaxin-1). Notably, mice deficient in
eotaxin-1/2, CCR3, and
IL-5 showed ablated esophageal
eosinophilia following cockroach or dust mite
allergen exposure. These data indicate that indoor insect
allergens are potent inducers of
IL-5 and eotaxin-mediated esophageal
eosinophilia. These experimental studies are in accordance with clinical data but may have some limitations inherent to animal models of human disease.