Anti-inflammatory oral immunotherapy for food allergy

ORSINI LUCíA; SMALDINI PAOLA; DOCENA GUILLERMO H.

Natal

Congreso; 11th World Congress on Inflammation y XXXVIII Congress of the Brazilian Society of Immunology; 2013

Introduction: Food allergy is a rising health concern worldwide and it is accepted that it is caused by a breakdown in immunologic tolerance. The most efficient treatment consists of the strict avoidance of exposure to food allergens. Since it is a complex task in patients younger than 2 years, new studies for corrective therapies are mandatory. Nowadays there is no standardized and approved immunointervention procedure. We aimed to induce oral tolerance to cow`s milk proteins (CMP) using CMP in an IgE-mediated food allergy mouse model. Methods: Balb/c mice were orally given CMP (CMPprev) prior to oral sensitization with CMP and cholera toxin (prevention), or after sensitization (desensitization) (CMPdes). Mice were orally challenged with CMP and the immune response was evaluated with in vitro (serum IgE, IgG1, IgG2a and IgA level; TNF-á, IL-6, IL-17A, IL-5, IL-13, IFN-ã, IL-10 and TGF-â secretion by spleen cells and Treg cells in the intestinal mucosa) and in vivo assays (clinical score and cutaneous tests). Histology was analyzed in gut specimens to evaluate the inflammatory infiltrate. Results: we found a lower medium clinical score in CMPprev and CMPdes mice after the oral challenge with CMP, as compared to sensitized mice, with a reduction in skin mast cell reactivity in tolerized mice. Immunological changes include decreased specific IgE (1,57±0,2 vs 0,87±0.2 CMPdes; 0,52±0,1 CMPprev) and IgG1 (2,07±0,7 vs 0,91±0,2 CMPdes; 0,11±0,05 CMPprev), decreased TNF-á, IL-6, IL-5 and IL-13 at the protein and mRNA level, and induction of IL-10-producing regulatory T cells in lamina propria of duoenum (1,02±0,3% vs 9,53±0,1% CMPdes; 10±0,4% CMPprev) and mesenteric lymph nodes in tolerized mice. TGF-â, IgG2a and IgA levels were not modified. A mild inflammatory infiltrate of mononuclear cells was observed in duodenum of sensitized mice, which was completely reverted in treated mice. Hypereosinophilia was also controlled. Conclusion: The oral immunotherapy with milk proteins down-modulated the allergic specific immune response in CMP-sensitized mice. This approach could provide a new therapeutic anti-inflammatory intervention for CMP food allergy, either for prevention or desensitization.