Over the last several decades, there has been a steady rise in the prevalence of food allergy and other allergic diseases in the U.S. and other industrialized countries. Of concern, the most rapid rise in food allergy has been observed in children. Whereas the prevalence of food allergy is 3-4% in the overall population, it is 6-8% among children. In addition, there has also been a concurrent rise in the severity of food allergy reactions resulting in a greater number of hospitalizations. Although environmental factors are thought to play a significant role in this alarming trend, the specific causative agent(s) remain to be identified. We recently demonstrated that tert-butylhydroquinone (tBHQ), a synthetic food additive present in many processed foods, promotes polarization of CD4 T cells towards the Th2 lineage, a key step in the development of allergy. Furthermore, our preliminary studies demonstrate that tBHQ, at concentrations relevant to human exposure, exacerbates food allergy in an animal model, suggesting a potential role for tBHQ in the increased prevalence of food allergy in humans. For these studies, we utilized a unique model of food allergy that is adjuvant-free and does not require injections. The animals are sensitized to food allergen via transdermal administration, which results in a rapid rise in plasma levels of IgE and IgG1, antibodies associated with allergic response. It is worth noting that infants and toddlers may also be sensitized to food allergen transdermally through prolonged skin contact to food proteins through diaper wearing. A key limitation of our preliminary studies is that they were conducted in adult animals, whereas the highest prevalence of food allergy occurs in children. Therefore, a major goal of this proposal is to determine the effect of tBHQ on the immune response to food allergen in juvenile animals. Our central hypothesis is that the synthetic food additive tBHQ increases IgE/IgG1 production and exacerbates anaphylaxis in juvenile animals in response to food allergen. This hypothesis is based upon our strong preliminary data showing that adult mice exposed to a low dose of tBHQ equivalent to that found in the human diet, have a markedly increased immune response to food allergen, as evidenced by increased plasma levels of IgE and IgG1, greater decrease in body temperature in response to oral challenge, increased concentrations of mMCP-1 in plasma, increased mast cell degranulation, among other effects. We propose to test our hypothesis by 1) developing and characterizing a model of food allergy in juvenile animals and 2) using that model to determine the effect of tBHQ on the immune response to food allergen in juvenile animals.
Over the last several decades, there has been a steady rise in the prevalence and severity of food allergy and other allergic diseases in the U.S. and other industrialized countries. Of concern, children seem to be particularly susceptible; the prevalence of food allergy in children is twice that of the overall population. Although environmental factors have been implicated, these have yet to be identified. Our preliminary data strongly suggest that the synthetic food additive tBHQ worsens anaphylaxis in response to food allergen in adult animals. The purpose of this project is to 1) develop a model of food allergy in juvenile animals and 2) to use that model to determine the effect of tBHQ on the immune response to food allergen in juvenile animals.
