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ToxSci Advance Access published online on September 19, 2008
Toxicological Sciences, doi:10.1093/toxsci/kfn200
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Published by Oxford University Press 2008.

Failure to Induce Oral Tolerance in Mice is Predictive of Dietary Allergenic Potency Among Foods with Sensitizing Capacity

Christal C. Bowman and MaryJane K. Selgrade

Immunotoxicology Branch, Experimental Toxicology Division National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711

Corresponding Author: Christal C. Bowman, US EPA/NHEERL, 109 T W Alexander Drive, MD B143-01, Research Triangle Park, NC 27711, e-mail: bowman.christal{at}epa.gov, phone: (919) 541-0152, fax: (919) 541-4284

Received July 18, 2008; revision received August 21, 2008; accepted September 11, 2008


  Abstract

Animal models are needed to assess novel proteins produced through biotechnology for potential dietary allergenicity. Currently proposed rodent models evaluate sensitizing potential of food extracts or proteins following parenteral administration or oral administration with adjuvant. However, food allergy requires not only the potential to induce IgE, but also the capacity to avoid induction of oral tolerance (specific inhibition of IgE production). Here we describe a mouse model that assesses the potential of food extracts to induce oral tolerance. Adult C3H/HeJ mice were exposed orally to food extracts (without adjuvant) and subsequently challenged with the extract intraperitoneally. Reduction of antigen-specific serum IgE relative to appropriate controls was used to indicate tolerance. Foods associated with persistent, severe allergy (peanut, Brazil nut) and non-allergens (turkey, spinach) were less tolerizing than foods associated with frequently resolving allergy (egg white). Digestibility was assessed in vitro, and pH alterations or encapsulation were used to modify solubility or digestibility. Egg white, peanut, and Brazil nut proteins were resistant to gastric enzyme (pepsin) degradation; turkey and spinach were not. Among pepsin-resistant proteins, peanut and Brazil nut appeared more sensitive to intestinal enzyme than egg white. For the extracts tested, full gastric digestion appeared to prevent induction of tolerance. Once through the stomach, only proteins resistant to intestinal enzymes induced tolerance. Limiting gastric digestion with sodium bicarbonate enhanced tolerance to peanut and Brazil nut. This model represents a complementary method of assessing potential allergenicity. Also, the conditions under which the test protein is encountered may impact experimental outcome.

Key Words: allergenicity; oral tolerance; food allergy; biotechnology; digestibility; genetically modified food.


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M. K. Selgrade, C. C. Bowman, G. S. Ladics, L. Privalle, and S. A. Laessig
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[Abstract] [Full Text] [PDF]


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