Asthma is characterized by obstructed airways and prolonged inflammation initiated and perpetuated by an influx of CD4+ immune cells. The CD4+ cell-specific chemoattractant cytokine, IL-6, has been shown to be expressed by airway epithelium in asthmatics and in mice following antigen sensitization. The IL-16 is then released rapidly following either antigen or histamine segmental challenge in asthmatics, and the elaboration of IL-16 alone following histamine challenge results in a two- to three-fold increase in T cells obtained by BAL. In addition to induced CD4+ cell chemoattraction, IL-16 stimulation of CD4+ T cells results in upregulation of the IL-2 receptor (IL-2R). The ability of IL-16 to recruit CD4+ cells to sites of inflammation and to induce IL-2R on responding lymphocytes matches the profile of infiltrating cells seen in the mucosa of asthmatic lungs. These observations indicate the presence and a potential role of IL-16 in the initiation of asthmatic inflammation. By no means is IL-16 the only cytokine or immune cell chemoattractant active in asthmatic inflammation; many cytokines have been identified and potential roles elucidated using a variety of animal models. The intriguing aspect of IL-16 is the early release following antigen challenge. This project is based on the hypothesis that IL-16 is an early mediator of CD4+ cell recruitment in the lung because it is synthesized during the sensitization phase and therefore primed for rapid release by antigenic or vasoactive amine stimulation. By virtue of its early release, IL-16 may be instrumental in the initiation of the cell recruitment seen in an asthmatic response. These studies are designed to: (1) define the conditions in the sensitization phase required to induce epithelial cell-derived IL-16; and (2) to determine the mechanism for IL-16's effect on IgE antibody production.
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