ToxSci Advance Access originally published online on September 19, 2008
Toxicological Sciences 2008 106(2):435-443; 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
Immunotoxicology Branch, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, U. S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711
1 To whom correspondence should be addressed at U. S. Environmental Protection Agency/National Health and Environmental Effects Research Laboratory, 109 T. W. Alexander Drive, MD B143-01, Research Triangle Park, NC 27711. Fax: (919) 541-4284. E-mail: bowman.christal{at}epa.gov.
Received July 18, 2008; accepted September 11, 2008
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Abstract |
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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 immunoglobulin (Ig) E 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 ip. 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 nonallergens (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.
Disclaimer: This report has been reviewed by the Environmental Protection Agency's Office of Research and Development and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the Agency nor does mention of trade names or commercial products constitute endorsement or recommendation for use.
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