This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In this project, we propose to 1) confirm the link between smoking, periodontal disease and biomarkers of the acute phase response as indicators of exaggerated systemic inflammation, and 2) test the effects of tetracyclines on circulating inflammatory cell function, biomarkers of periodontal disease, and the acute phase markers of systemic inflammation in smokers as well as smoke-exposed animal models. Our hypothesis is that the tetracyclines will lower the levels of the markers of systemic inflammation as they reduce the severity of periodontitis. Because the Phase I studies on CMT-3 are not yet complete, we propose initially to treat a cohort of human smokers with periodontal disease with a subantimicrobial dose of doxycycline (Periostat ), adjunctive to routine standard of periodontal management as currently recommended, and evaluate their response through a panel of biomarker assays which can be performed with minimal invasiveness.
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