This project seeks to develop novel immunologic therapies for allergic diseases as well as the laboratory techniques required to understand their mechanisms of action and rational application. We are presently performing a clinical trial examining the immunological effects of allergen immunotherapy by monitoring allergen specific T cell responses. The hypothesis of this work is that allergen immunotherapy works via tolerance (a decrease in allergen specific T cells) rather than via a Th2 to Th1 shift. Understanding the immunological mechanisms of allergen immunotherapy is a requisite for developing new more effective antigen specific therapies. Eosinophilic gastroenteritis is a severe inflammatory disease of the gut, characterized by dense tissue eosinophil infiltration and is often associated with atopy and food allergy. In these food allergic subjects, eosinophilic gastroenteritis appears to be a severe manifestation of food allergy and as such, provides a model system in which to examine questions relating to the pathogenesis of food allergy. To examine the role of IL-5 in subjects with eosinophilic gastroenteritis and food allergy, we are engaged in a clinical trial using SCH55700, a humanized anti-IL-5 monoclonal antibody. Interim results demonstrate that a single dose of SCH55700 yielded a rapid 80% drop in peripheral blood eosinophil counts within 48 hours and that after one month gastrointestinal eosinophils were decreased by 50-70% in 3 of 4 subjects. These data demonstrate that both the peripheral blood and tissue eosinophilia found in EG are responsive to IL-5 blockade.
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