Purpose of Study. An experimental model was established to test the hypothesis that eosinophilic esophagitis is mechanistically linked to eosinophilic allergic responses in the lung.
Study Population. Eight- to 10-week-old BALB/c mice, interleukin (IL)-5 gene-targeted mice, and eotaxin-deficient inbred mice were maintained with age- and sex-matched controls.
Methods. Using previously published protocols, mice were exposed to repeated inoculations of Aspergillus fumigatus antigens by oral, intragastric, and intranasal routes. Eosinophils levels in the esophagus were analyzed by anti-major basic protein immunostaining. The tissue distribution of eosinophils after intranasal allergen was examined in the blood, bronchoalveolar lavage fluid, stomach, and small intestine. Pathologic changes were defined using histologic examination of the esophagi and electron microscope analysis of tissue eosinophil morphology. Experimental eosinophilic esophagitis was induced in eotaxin gene-targeted mice and in IL-5 gene-targeted mice.
Results. Allergen-challenged mice developed marked levels of esophageal eosinophils, free eosinophil granules, and epithelial cell hyperplasia, which mimic pathophysiologic changes observed in humans with eosinophilic inflammation of the esophagus. Of note, eosinophil levels in the stomach and small intestine did not significantly increase after allergen challenge. As opposed to the intranasal route, exposure of mice to oral or intragastric allergen does not promote eosinophilic esophagitis, indicating that hypersensitivity in the esophagus occurs with simultaneous development of pulmonary inflammation. In the absence of eotaxin, eosinophil recruitment is attenuated, and furthermore, in the absence of IL-5, eosinophil accumulation and epithelial hyperplasia were ablated.
Conclusions. These results establish a pathophysiologic connection between allergic hypersensitivity responses in the lung and esophagus and demonstrate an etiologic role for inhaled allergens and eosinophils in gastrointestinal inflammation. Moreover, these investigations dissect the cellular and molecular mechanisms involved in eosinophil homing into the esophagus. Aeroallergens may be contributing to the pathogenesis of esophageal inflammation in a subset of patients with primary eosinophilic esophagitis and gastroesophageal reflux disorders.
Reviewer’s Comments. Just when you thought you had heard of the last potential trigger for gastroesophageal reflux disorders, this very provocative investigative model of experimental eosinophilic esophagitis was published. These data suggest that eosinophilic esophagitis can be mediated by extrinsic allergens and establish a causal link between the development of allergic hypersensitivity in the respiratory tract and in the esophagus. This model not only implicates a role for aeroallergens in the pathogenesis of esophagitis, but also provides a novel system to evaluate the treatment of eosinophilic esophageal disorders, which include gastroesophageal reflux, allergic eosinophilic esophagitis, eosinophilic gastroenteritis, primary eosinophilic esophagitis, and drug reactions.
- Copyright © 2002 by the American Academy of Pediatrics