Induction and suppression of allergic diarrhea and systemic anaphylaxis in a mouse model of food allergy. (163.21)

Abstract

Abstract We evaluated the requirements for development of allergic diarrhea (AD) and anaphylactic shock (AS) in response to Ag ingestion and whether ingested Ag must be absorbed systemically to trigger these responses. TNP-BSA ingestion induced AS without AD in IgE anti-TNP mAb-primed, immunologically naïve wild-type mice and intestinal IL-9 transgenic mice, even though the latter mice have intestinal mastocytosis, but both AS and AD in IgE anti-TNP mAb-primed mice that had recently been immunized i.p., then p.o. with ovalbumin (Ova). Mice inoculated once i.p. with Ova/alum, then multiple times p.o. with Ova, develop both AD and AS in response to oral Ova challenge; a second i.p. Ova/alum inoculation prevents AS, but not AD. J chain- and pIgR-deficient mice, which have increased serum IgA and decreased gut IgA, are relatively resistant to development of AD. Treatment of IgE anti-TNP mAb-primed, Ova-immunized mice with i.v. IgG anti-TNP mAb inhibits both AD and AS responses to oral TNP-BSA challenge, with AS more sensitive to inhibition. We conclude that: 1) induction of AD, but not AS, by ingested Ag requires local Ag-induced changes to the intestinal immune system beyond mast cell and IgE induction; 2) ingested Ag must be systemically absorbed to induce both AD and AS; and 3) more ingested Ag must be absorbed systemically to induce AS than to induce AD. These observations suggest that induction of a systemic IgG Ab response can suppress established food allergy.