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. This NIH funded study is based on the premise that macrophage responses to bacterial lipopolysaccharides (LPS) mediate the progression and severity of periodontal disease through elevated production of pro-inflammatory cytokines (e.g. TNF-a, IL1b, and PGE2). The study focuses in particular on diabetic patients because periodontal disease is excessive among these patients, and cytokine responses associated with progression of periodontal disease have been shown to be markedly higher in diabetic patients than those observed in non-diabetic individuals. 200 patients, ages 21-65, with diabetes, with and without periodontal disease defined by standard criteria, will be recruited to the study. Background demographic information concerning medical and dental histories and medications will be obtained from study patients. One-time, 50 mL venous blood samples will be drawn from each patient, and monocytes and LPS will be isolated from these samples for laboratory studies of phagocytic cell activation and LPS stimulation of monocyte/macrophages. In addition, portions of this blood sample will be used for genetic studies of polymorphisms in the IL-1 gene cluster for the sake of identifying relationships, if any, between polymorphisms and the occurrence of periodontitis in diabetic individuals. Finally, bacteria and periodontal fluid samples will be obtained from periodontal pockets to characterize the microorganisms present in the periodontal tissues of patients and to measure cytokine levels at the