PATHOGENESIS OF ASTHMA

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DESCRIPTION: (Adapted from Investigator's abstract): This is a new application from a very experienced investigator that proposes to examine the relative contributions of basophils and T-lymphocytes in the production of IL-4, IL-5 and IL-13 during the initiation and maintenance of the allergic airway inflammation. Cytokine gene expression and protein production by bronchoalveolar lavage cells and in bronchial biopsies obtained from asthmatic subjects will be examined at varying times after allergen challenge. The cell source for each cytokine will be determined by in situ hybridization, immunohistochemistry in biopsies, and by FACS analysis and functional studies in BAL cells. The investigators hypothesize that after allergen exposure, basophils are recruited rapidly to the airways and are the initial major source of IL-4 and IL-13, while T lymphocytes are recruited more slowly and represent the major source of IL-5. The investigators also hypothesize that a newly described cytokine, histamine releasing factor (HRF), plays a central role in asthma by activating the infiltrating basophils and eosinophils. Therefore they will assess HRF levels and determine the cellular location of HRF after airway challenge and in acute and chronic asthmatic episodes.