Interleukin-17 mediated inflammation in COPD

DESCRIPTION (provided by applicant): Novel therapeutic targets for the treatment of chronic obstructive pulmonary disease (COPD) are urgently needed, as the incidence of COPD - a chronic inflammatory lung disease that imposes tremendous economic burden on the health care system - is increasing worldwide. Limited therapeutic options exist for patients with established COPD, and the role of immune-modulatory therapy is unclear, despite the fact that chronic inflammation - particularly neutrophil influx - is a cardinal feature of the chronic phase and acute exacerbations of COPD. This application will specifically address the role of interleukin-17 (IL-17) in the pathogenesis of COPD. Ineterleukin-17 belongs to a recently described family of cytokines that coordinate local tissue inflammation by inducing the release of several pro-inflammatory cytokines and chemokines, including potent neutrophil chemoattractants. The central hypothesis tested by this application is that COPD is associated with excessive T cell derived IL-17, which correlates with severity of COPD. This central hypothesis is supported by numerous lines of scientific evidence, including murine models of IL- 17 overexpression in which some of the cardinal phenotypic features of human COPD may be reproduced. The central hypothesis will be tested in two related specific aims. In specific aim 1 we will determine the production of Th-17 polarizing cytokines and cellular sources of IL-17 production in COPD tissue. In specific aim 2, we will correlate quantitative IL-17 levels in COPD tissue with functional and radiographic indices of obstructive lung disease, and other clinical parameters, through utilization of the unique data procured through the lung tissue research consortium (LTRC). The studies proposed in this application are aimed at the identification of novel therapeutic targets with the capacity to mitigate the chronic inflammatory cascade and lung remodeling in COPD. PUBLIC HEALTH RELEVANCE: Novel therapies for chronic obstructive pulmonary disease (COPD) - a chronic inflammatory lung disease that imposes tremendous economic burden on the United States health care system - are urgently needed. This application will specifically address the role of the inflammatory protein, interleukin-17 (IL-17) in the pathogenesis of COPD. Ineterleukin-17 belongs to a recently described family of inflammatory proteins that can induce tissue inflammation, and promotes mucus secretion by glands in the airways. The studies proposed in this application are aimed at the identification of novel treatment approaches for COPD. (End of Abstract)