MODULATION OF AIRWAY EPITHELIAL CELL CYTOKINE PRODUCTION

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Airway epithelial cells release a variety of proinflammatory cytokines by which they may modulate the airway inflammatory process. Prior studies have documented the ability of proinflammatory cytokines to induce airway epithelial cell production of cytokines such as Interleukin-6(IL-6), Interleukin-8(IL-8) and GM-CSF. Airway neuropeptides and peptides may also modulate airway epithelial cell responses. Therefore, it was of interest to study the effect of airway neuropeptides and other airway peptides on airway cytokine production. Vasoactive intestinal peptide(VIP) is a neuropeptide of the nonadrenergic noncholinergic nervous system. VIP added to an airway epithelial cell line induces production of IL-6 and IL-8. Similarly, Endothelin-1 added to an airway epithelial cell line induces production of IL-6 and IL-8. Studies of changes in epithelial cell steady state mRNA levels for IL-6 and IL-8 in response to VIP and Endothelin-1 as well as other mediators locally produced in the airway are in progress. Knowledge of the mechanisms by which epithelial cell cytokine production may be modulated may allow for a better understanding of the pathophysiology of inflammatory lung diseases.