IgE and mast cell responses on intestinal allergen exposure: A murine model to study the onset of flood allergy

Objective: Allergic reactions to food are characterized by enhanced allergen-specific IgE serum levels and the activation of intestinal mast cells. Here we describe a murine model for the onset of food allergy and the role of cytokines in the regulation of food-induced IgE responses. Methods: Mice are primed systemically with low doses of alum-precipitated ovalbumin. Subsequent intragastric challenge led to enhanced sensitization. Results: Compared with baseline ovalbumin-specific IgE levels before challenge (0.23 ± 0.06 optical density [OD] units, ovalbumin-challenged mice showed significantly elevated IgE levels (0.86 ± 0.23 OD units) after intragastric challenge, which were not observed in control animals (0.29 ± 0.06 OD units). IgE levels mirrored intestinal mast cell activation, measured by decreased histamine levels in duodenal specimens, in ovalbumin-challenged mice (92.6 ± 7.9 ng/0.1 gm tissue weight) but not in saline-challenged mice (135.4 ± 18.3 ng/0.1 gm tissue weight), compared with baseline levels (141.1 ± 4.1 ng/0.1 gm tissue weight). Changes in IgE and histamine levels after intragastric challenge could be blocked by treating the animals with neutralizing antibodies against IL-4 or IL-10. Although it is generally accepted that ingestion of food allergens leads to a state of immunologic unresponsiveness (i.e., oral tolerance), it is shown here that low-dose systemic priming followed by intragastric challenge leads to sensitization instead of unresponsiveness. Conclusions: Our murine model shows an important correlation between T(H2) cytokines, IgE production, and histamine release. Hence, this in vivo model provides a useful tool with which the complex mechanism underlying sensitization of food allergens can be studied.