The asthmatic diathesis is characterized by chronic airway inflammation. In vivo and in vitro studies have demonstrated the disregulation of a wide variety of cytokines in the asthmatic airway. However, in most circumstances, the ability of individual cytokines to mediate the pathologic and physiologic derangements characteristic of this disorder are poorly understood. to address this issue, we have developed a system that allows us to express cytokines in the murine airway in an organ-specific fashion. When this was done with human interleukin-11, prominent abnormalities were noted. They included: a) peribronchiolar nodular inflammatory infiltrates, b) subepithelial fibrosis with airway remodeling; c) emphysema in alveolar areas; and d) airways hyper-responsiveness to methacholine. To further understand the morphology of the airways of these mice, we propose to use the Center for In Vivo Microscopy to characterize the airways of transgene (+) and transgene (-) animals. It is hoped that this approach will enable us to differentiate remodeling from hypoplasia. The effects of other cytokines on airway development and structure will be analyzed in a similar fashion.
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