IgE and mast cell response on intestinal allergen exposure: a murine model to study the onset of food allergy.

Abstract

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. Mice were primed systemically with low doses of alum-precipitated ovalbumin. Subsequent intragastric challenge led to enhanced sensitization. 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. Our murine model shows an important correlation between TH2 cytokines, IgE production, and histamine release. Hence, this in vivo model provides a useful tool with which the complex mechanism underlying sensitization to food allergens can be studied.