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EMERGING ISSUES: FOOD ALLERGIES, AUTOIMMUNITY, AND THE DEVELOPING IMMUNE SYSTEM

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vaccines to promote immunogenicity. There is now growing concern that chemicals in our environment (particularly, air pollutants) might act as adjuvants for allergic sensitization to common allergens such as dust mite and pollen. Laboratory rodents have been used to show that nitrogen dioxide, residual oil fly ash, and diesel exhaust enhance allergic sensitization and disease. Enhanced sensitization to an allergen has also been demonstrated in rhesus monkeys exposed to ozone and humans exposed to diesel exhaust. The significance of these findings in terms of enhanced burden of respiratory allergies in the human population is unclear. As in other areas of toxicology, simultaneous environmental exposures to agents that are not the agent of immediate concern can certainly influence outcomes. Adjuvancy is a concern that likely extends beyond air pollution and type 1 responses.

19.6 EMERGING ISSUES: FOOD ALLERGIES, AUTOIMMUNITY, AND THE DEVELOPING IMMUNE SYSTEM

There are several emerging issues in immunotoxicology. These active areas of research will be only briefly described here because there are currently more questions than answers.

Toxicologists have recently been drawn into the area of food allergy by advances in biotechnology and the need to assess the safety of genetically modified foods in terms of potential allergenicity. There is concern that insertion of a novel gene into a food crop (e.g., to increase yield or pest resistance) might inadvertently introduce a new allergen into the food supply. Food allergies are relatively rare, affecting approximately 5% of children and 2–3%of adults, and even in these individuals, most proteins are not food allergens. However, when food allergy does occur, the consequences can be severe. Anaphylactic(life-threatening)reactions to peanuts provide the best example. Unfortunately, the mechanisms underlying food allergies (or the mechanisms that protect most of people from developing reactions to the foreign proteins they eat), the characteristics that make a protein a food allergen, and the characteristics that make an individual susceptible to food allergies are poorly understood at this time. These are some of the issues that need to be resolved in order to develop appropriate safety assessment tools.

Autoimmune diseases affect about 3% of the population and comprise a diverse array of both organ specific (e.g., type I diabetes, thyroiditis) and systemic (systemic lupus erythematosis) diseases. Susceptibility includes a strong genetic component, and in some cases women appear to be more vulnerable than men. Xenobiotics might affect the development or progression of autoimmune disease. A variety of mechanisms could contribute to xenobiotic effects on the development and maintenance of immune tolerance or unmasking or modification of self proteins. There is evidence that exposure to certain drugs, heavy metals, silica, and endocrine disruptors are a concern in this regard. Current research includes both human and animals studies to determine the extent of risk and ways to assess and control it.

Finally there is growing concern that the developing immune system may be particularly vulnerable to xenobiotic exposures and that perinatal and/or in utero exposures may have a lifelong impact on susceptibility to infectious, allergic, or autoimmune disease. As in other areas of toxicology, tests designed to assess the risk of immunotoxicity for adults may not be sufficient to protect children and research is currently underway to determine how best to meet this need.

342 IMMUNOTOXICITY

Clearly, exposure to xenobiotics can have a number of effects on the immune system that in turn can affect an array of health outcomes. In some areas of immunotoxicology significant progress has been made in terms of identifying and understanding the risks associated with xenobiotic exposure. In other areas more research is needed.

SUGGESTED READING

Benjamini, E., G. Sunshine, and S. Leskowitz. Immunology A Short Course, 4th ed. New York: Wiley, 2000.

Gilmour, M. I., M. J. K. Selgrade, and A. L. Lambert. Enhanced allergic sensitization in animals exposed to particulate air pollution. Inhalation Toxicol. 12 (suppl. 3):373–380,2000.

Kimber, I., I. L. Bernstein, M. H. Karol, M. K. Robinson, K. Sarlo, and M. J. K. Selgrade. Workshop overview: Identification of respiratory allergens. Fundam. Appl. Toxicol. 33:1–10,1996.

Luster, M. I., A. E. Munson, P. T. Thomas, M. P. Holsapple, J. D. Fenters, K. L. White, L. E. Lauer, D. R. Germolec, G. J. Rosenthal, and J. H. Dean. Development of a testing battery to assess chemical-inducedimmunotoxicity: National Toxicology Program’s guidelines for immunotoxicity evaluation in mice.Fundam. Appl. Toxicol. 10:2–19,1988.

Luster, M. I., et al. Risk assessment in immunotoxicology I. Sensitivity and predictability of immune tests. Fundam. Appl. Toxicol. 18:200–210,1992, and II. Relationships between immune and host resistance tests.Fundam. Appl. Toxicol. 21:71–82,1993.

Metcalfe, D. E., et al. Assessment of the allergenic potential of foods derived from genetically engineered crop plants. Crit. Rev. Food Sci. Nutr. 36S:S165–S186,1996.

Roitt, I. Roitt’s Essentials in Immunology. London: Blackwell, 2001.

Sailstad, D. M. Murine local lymph node assay: An alternative test method for skin hypersensitivity testing. Lab. Animal 31:36–41,2002.

Sarlo, K. Human Health Risk Assessment: Focus on Enzymes. In Proceeding of the 3rd World Conference on Detergents, A. Cahn, ed. Champaign, I: Am. Oil Chem. Soc. Press, 1994, pp.54–57.