A trend of increase in periodontal interleukin-6 expression across patients with neither diabetes nor periodontal disease, patients with periodontal disease alone, and patients with both diseases.

BACKGROUND AND OBJECTIVE: Epidemiological studies have established that patients with diabetes have increased prevalence and severity of periodontal disease. However, the periodontal expression of inflammatory cytokines and matrix metalloproteinases (MMPs) in diabetic patients has not been well characterized. The objective of this study was to determine the difference in the periodontal expression of MMP-1, MMP-8, interleukin-6, tumor necrosis factor-alpha and interleukin-1beta between diabetic and nondiabetic patients. MATERIAL AND METHODS: Periodontal tissue specimens were collected from nine nondiabetic patients without periodontal disease (group 1), from 11 nondiabetic patients with periodontal disease (group 2) and from seven diabetic patients with periodontal disease (group 3). The expression of MMP-1, MMP-8, interleukin-6, tumor necrosis factor-alpha and interleukin-1beta was quantified using real-time polymerase chain reaction. RESULTS: The nonparametric Kruskal-Wallis test showed that the difference in interleukin-6 expression among the groups was statistically significant (p = 0.04). Furthermore, the generalized Kruskal-Wallis nonparametric linear-by-linear association test showed a statistically significant trend of increase in the expression of interleukin-6 from group 1 to group 2 to group 3 (p = 0.02) and a suggestion of such a trend for MMP-1 (p = 0.05). No increase in MMP-8 expression was observed in patients in group 3 compared to patients in groups 1 and 2. Although the average expression levels of MMP-1, interleukin-1beta and tumor necrosis factor-alpha were increased from group 1 to group 3, the differences were not statistically significant. CONCLUSION: A trend of increased interleukin-6 expression in periodontal tissues was observed across patients with neither diabetes nor periodontal disease, patients with periodontal disease alone, and patients with both diseases.

High glucose-boosted inflammatory responses to lipopolysaccharide are suppressed by statin.

BACKGROUND AND OBJECTIVE: It has been established that periodontal diseases are more prevalent and of greater severity in diabetic patients than in nondiabetic patients. Recent studies have underscored the role of monocytes and macrophages in periodontal tissue inflammation and destruction in diabetic patients. Although it has been shown that monocytes isolated from diabetic patients produce more inflammatory cytokines and that gingival crevicular fluid collected from diabetic patients contains higher levels of inflammatory cytokines than that obtained from nondiabetic patients, the underlying mechanisms are not well understood. MATERIAL AND METHODS: U937 histiocytes cultured in medium containing either normal (5 mM) or high (25 mM) glucose were treated with 100 ng/ml of lipopolysaccharide for 24h. After the treatment, cytokines in the medium and cytokine mRNA in the cells were quantified using enzyme-linked immunosorbet assay and real-time polymerase chain reaction, respectively. RESULTS: In this study, we demonstrated that the pre-exposure of U937 histiocytes to high glucose concentrations markedly increased the lipopolysaccharide-induced secretion of pro-inflammatory cytokines and chemokines and the cellular inducible nitric oxide level compared with pre-exposure to normal glucose. Our data also showed that the increased secretion of cytokines was a result of increased mRNA expression. Furthermore, the effects of statin and peroxisome proliferators-activated receptor agonists on high glucose-enhanced secretion of cytokines were determined. The results showed that simvastatin, but not fenofibrate or pioglitazone, inhibited high glucose-enhanced cytokine release. CONCLUSION: This study has shown that high glucose concentrations and lipopolysaccharide act synergistically to stimulate the secretion of inflammatory mediators, and that statin is capable of suppressing the high glucose-boosted proinflammatory response. This study therefore delineates a novel mechanism by which hyperglycemia enhances the inflammatory responses of macrophages and suggests that statin may be useful in the treatment of periodontal disease in diabetic patients.