This competitive renewal will continue to explore the role of IL-16 in CD4+ cell accumulation in human atopic asthma. In the current grant period we found that IL-16 is the major lymphocyte chemoattractant released early after segmental airway antigen challenge; that the epithelium of atopic asthmatics preferentially expresses IL-16 mRNA and protein; and that the degree of epithelial expression of IL-16 correlates with the extend of CD4+T cell accumulation and airway reactivity. We have recently observed that glucocorticoids inhibit IL-16 expression in epithelium and that IL-9 induces IL-16 expression in human epithelial cells in vitro. This is the first demonstration of any epithelial functions in response to IL-9 and identifies an entirely new class of functions for this Th2 cytokine. Thus, we hypothesize that airway epithelial IL-16 expression is up-regulated by cytokines (i.e. IL-9) and inhibited by glucocorticoids and that IL-16 serum levels will correlate with disease activity. Our aims are to: 1). Identify the IL-9 and glucocorticoid response regulatory elements in the IL-16 promoter; 2). Determine the factors responsible for epithelial cell secretion of IL-16 and: 3). Correlates IL-16 serum levels with experimental and naturally occurring exacerbations of asthma.