EFFECTS OF TETRACYCLINES ON ACUTE PHASE PROTEINS IN SMOKERS W PERIODONTITIS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。在本项目中，我们建议1)确认吸烟、牙周病和急性期反应生物标志物之间的联系，作为全身性炎症夸大的指标；2)在吸烟者和吸烟暴露动物模型中测试四环素对循环炎症细胞功能、牙周病生物标志物和全身性炎症急性期标志物的影响。我们的假设是，四环素会降低全身性炎症标志物的水平，因为它们降低了牙周炎的严重程度。由于CMT-3的I期研究尚未完成，我们建议首先用亚抗菌剂量的多西环素（Periostat¿）治疗一组患有牙周病的人类吸烟者，辅助目前推荐的常规牙周管理标准，并通过一组生物标志物检测来评估他们的反应，这些检测可以以最小的侵入性进行。

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.