This project is a continuation of studies that focus on the local neural and cellular regulation of nasal function utilizing both immunologic and non-immunologic challenge. In the present proposal, the main hypothesis is that the genes encoding the cytokines IL-1-alpha, IL-1-beta, IL-8, and TNF- alpha are expressed in a sequential and non-random manner during the different stages of the inflammatory response to antigen presentation to the nose. In situ hybridization analysis will be used to determine whether cytokine gene expression in the nasal mucosa is affected by antigen presentation. Furthermore, since each cytokine has multiple but distinct activities, it is postulated that expression of cytokine genes will occur at different times following acute antigen exposure or show different patterns of expression in chronic airway disease, such as rhinitis and asthma, in which continued inflammation is believed to occur in the respiratory mucosa. Studies, to be performed in human subjects, are proposed along five specific aims: 1) To determine the cellular localization and relative abundance of these cytokines in the nasal mucosa of healthy subjects, 2) To assess the sequence of cytokine gene expression in response to relevant and irrelevant antigen challenge in subjects with allergic rhinitis, 3) To assess the effect of clinically useful topical agents (corticosteroid, cromolyn, and antihistamine) on cytokine gene expression in response to relevant antigen challenge, 4) To compare the cellular localization and relative abundance of nasal cytokine gene expression between patients with active allergic rhinitis and those with non-allergic rhinitis, and 5) To characterize the nasal and bronchial cytokine gene expression in asthmatic patients. Results from these studies will provide new information on the presence and localization of gene expression for four important cytokines involved in the protective and inflammatory responses of the respiratory mucosa.
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