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Research Interests
- Pathogenesis and treatment of allergic diseases.
Past Research
In the 1960's my work with T. P. King demonstrated that most of the allergenic activity of ragweed pollen resided in a single species of protein that Dr. King called Antigen E. Since then the protein has been renamed Amb a 1. This protein has become the basis for standardization of extracts of ragweed pollen used for allergic diagnosis and treatment. Work with L. M. Lichtenstein employed studies of histamine release from basophils of allergic patients. In ragweed allergic people the sensitivity of basophils to Amb a 1 could predict the severity of hay fever during natural exposure to ragweed pollen. Allergy shots (or immunotherapy, a new name we suggested) altered histamine release responses and raised antibodies that inhibited histamine release.
With W. L. Winkenwerder, we found that a steroid drug, dexamethasone, locally applied in the nose several times a day would greatly improve the symptoms of hay fever with minor side effects. With R. R. Rosenthal, we developed a method for quantitative challenge of the airways with aerosols of allergen extracts and showed that the degree of response could be related to severity of disease. This method has been used to test the efficacy of many antiasthmatic drugs. Immunotherapy also minimizes the severity of the response.
With R. M. Naclerio, we developed a similar technique for nasal challenge. Sampling of nasal secretions during the allergic response demonstrated appearance of mast cell and basophil mediators such as histamine and leukotrienes. Kinins also appear in the secretions. With P. S. Creticos we found that immunotherapy inhibited these responses.
Work with allergoids, allergens modified by formaldehyde in a method developed by D. G. Marsh showed that they could be successfully used as a form of immunotherapy.
Current Research
My research has been directed toward understanding the mechanisms of immunotherapy, i.e. the subcutaneous administration of allergenic substances that builds up resistance to further exposure in the respiratory tract to the same allergen. Allergic responses have two phases: an immediate mediator release phase, presumably triggered by cross-linking of IgE antibodies on mast cells; and a late phase of inflammatory response with basophils and eosinophils that many think is the result of cytokine elaboration by T cells specific for allergen.
Research thus far has demonstrated that immunotherapy does relatively little to reduce the amount of IgE antibodies available for mast cell mediator release although there is a modest change. On the other hand, T cell proliferation and cytokine secretion by allergen-specific T cells has been shown in several laboratories to be diminished after immunotherapy. Furthermore, when we have looked specifically at late phase responses to challenges with allergens, the magnitude of the clinical response, the amount of mediator release, and the infiltration with eosinophils has been reduced.
Laboratory
Philip S. Norman, MD
Professor- senior laboratory investigator
Positions available
None
Last Updated: 6/1/05
