Adipokines and myeloid cell immune responses in periodontal disease and diabetes

Abstract

Type 2 diabetes mellitus (T2DM) is a risk factor for periodontal disease, however the pathogenic links between the two diseases are not completely understood. Both diseases are considered to be inflammatory conditions and, therefore, immune mediators likely play a role in the shared susceptibility between two diseases. Adipokines have numerous immunological properties and their concentrations are altered in diabetes. Myeloid cells are key leukocytes in responses to periodontal pathogens such as Porphyromonas gingivalis. Therefore, the present study aimed to investigate the role of leptin and adiponectin in myeloid cell immune responses and in T2DM patients as potential mediators in an immunological link between diabetes and periodontal disease. Leptin increased both E. coli and P. ginivalis LPS-induced TNF-α expression in monocytes. Although leptin had no effect on TLR4 expression, leptin did upregulate TLR2 and enhanced monocyte differentiation. Together, these results indicate the potential of leptin to alter monocyte immune responses to periodontal pathogens. Male but not female T2DM patients with gingivitis of chronic periodontitis had increased serum leptin concentrates in comparison to matched, non-diabetic controls. Serum adiponectin concentrations were not effected by periodontal status. In contrast, gingival crevicular fluid (GCF) adiponectin concentrations were higher in periodontal disease in both T2DM patients and non-diabetic controls. GCF adiponectin concentrations were a predictor of periodontal status independent of BMI or gender. Serum adipokine concentrations were not affected by periodontal treatment. A decrease on GCF adiponectin concentrations was observed in T2DM patients and non-diabetic controls after periodontal treatment. In conclusion, findings of the present study demonstrate a role for leptin in monocyte differentiation and immune responses towards periodontal pathogens. In addition, analyses of clinical samples revealed that leptin and adiponectin are a potential link between diabetes and periodontal disease. In particular, GCF adiponectin concentrations may represent a diagnostic marker for diabetes and periodontal disease.