Date of Award
Master of Science (MSc)
Elena Verdu, Susan Waserman
It has been suggested that environmental factors substantially contribute to the increased prevalence of peanut allergy in industrialized countries. Specifically, the role of disrupted barrier integrity in the gastrointestinal tract has been implicated in the development of food allergy. The use of non-steroidal anti-inflammatory drugs (NSAIDs), which increase intestinal permeability, for the treatment of pain and fever is prevalent in industrialized countries. Therefore, the first aim of this study was to determine whether treatment with indomethacin, a prototypical NSAID, would act in an adjuvant like manner to facilitate sensitization to co-administered peanut protein. Furthermore, we investigated whether indomethacin increases susceptibility to anaphylaxis following oral challenge with peanut in sensitized mice.
First, a short model of cholera toxin-mediated sensitization to peanut was developed. Mice were given 1 mg of peanut protein and 5 μg of cholera toxin by oral gavage for 10 consecutive days. This resulted in a robust anaphylactic response and increased peanut-specific IgG1, but not IgE, two weeks following treatment. Mice exposed to peanut during a 10-day treatment with indomethacin (5 mg/kg on alternating days or 3.5 mg/kg daily) did not develop peanut-specific immunoglobulins or anaphylaxis following systemic challenge with peanut protein. Furthermore, treatment with two 5 mg/kg doses of indomethacin 24 and 1 hour before oral challenge did not facilitate anaphylaxis in peanut-sensitized mice. Therefore, we concluded that NSAID treatment is unlikely to play a role in the increased prevalence of peanut allergy, and that NSAID treatment does not increase susceptibility to peanut-induced anaphylaxis in sensitized mice.
The second part of this study aimed to develop a short model of epicutaneous sensitization, and address the impact of epicutaneous exposure to peanut during infancy. We investigated the role of site of exposure, duration of exposure, epidermal integrity, strain and age in epicutaneous sensitization. 10 consecutive days of epicutaneous exposure to 20 μg of peanut protein through tape stripped skin induced robust anaphylaxis following i.p. challenge. Neither 7 days of exposure through tape stripped skin, nor 10 days of exposure through intact skin facilitated sensitization. The strength of sensitization was strain-dependent; peanut-specific IgG1 was increased equally in both C57BL/6, and BALB/c mice, and to a greater extent in C3H/HeJ mice. Peanut-specific IgE was increased in both BALB/c and C3H/HeJ mice three weeks following peanut exposure. Epicutaneous exposure beginning one day after birth did not facilitate the development of either peanut-specific IgE or IgG1 in BALB/c mice, or anaphylaxis following systemic challenge. Beginning exposure at 2 weeks of age resulted in peanut-specific IgE and IgG1 production, as well as a robust anaphylaxis following i.p. challenge. Therefore, the development of peanut allergy through epicutaneous exposure is age dependent, and exposure during the neonatal period results in a hyporesponsive response.
Flader, Kristin A., "IMPACT OF GASTROINTESTINAL AND SKIN BARRIER DISRUPPTION ON SENSITIZATION TO PEANUT" (2012). Open Access Dissertations and Theses. Paper 7519.
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Available for download on Thursday, September 26, 2013