DELIVERY OF THE INTERLEUKIN-1 TYPE II GENE TO LUNG

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DESCRIPTION (Adapted from the applicant's abstract and specific aims): This project proposes to define the role of the interleukin-1 type II receptor (IL-1 IIr) in neutrophil recruitment to lung tissue during inflammation. An in vitro model using relevant rat lung cells will be studied to determine the influence IL-1b neutralization via gene delivery has on cytokine induced neutrophil chemottractant (CINC) chemokine production and neutrophil chemotaxis. Additionally, the utility of IL-1 Iir gene expression in vivo in an acute neutrophilic alveolitis model in rat lung will be explored. The specific aims are: 1) to induce the production of soluble IL-1 IIr protein in relevant rat lung cells in culture by delivery of the human IL-1 IIr gene; 2) to determine if over-expression of soluble IL-1 IIr can inhibit IL-1b mediated chemotaxis of neutrophils in vitro; and 3) to over-express IL-1 IIr in lung tissue in vivo and test the influence on neutrophil migration into lung tissue following endotoxin challenge.