Obesity is a significant predictor of periodontal disease and insulin resistance appears to mediate this relationship. Furthermore, obesity is associated with high plasma levels of TNFalpha and its soluble receptors, which in turn may lead to a hyperinflammatory state increasing the risk for periodontal disease and also accounting in part for insulin resistance. Further studies of the molecular basis of insulin resistance and its relationship to diabetes, periodontal disease, and obesity are necessary to fully test the hypothesis that adipocyte production of proinflammatory cytokines is a pathogenic factor linking obesity to diabetes and periodontal infections.

The results indicate that anti-infectious treatment is effective in improving metabolic control in diabetics, possibly through reduced serum TNF-alpha and improved insulin resistance.

It is generally accepted that obesity is associated with many other multiple-risk factor syndromes such as hypertension, hyperlipidemia, type 2 diabetes mellitus, and periodontal disease. The number of obese people is increasing rapidly in both western and eastern countries. Adipocytes in the adipose tissues of obese people produce large quantities of biologically active molecules such as leptin, an important molecule regulating energy expenditure and body weight. Therefore, adipocyte-derived active molecules, named adipocytokines, are candidate molecules accounting for the close association between obesity and other multiple-risk factor syndromes. The proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) is produced by adipocytes, and its blood concentration is elevated in obese patients and declines with weight loss. Studies have demonstrated that TNF-alpha suppresses insulin action via its specific receptor; hence, it exacerbates insulin resistance. In addition to adipocytes, monocytes/macrophages produce large quantities of TNF-alpha. Thus, TNF-alpha, produced from monocytic cells due to inflammatory diseases, may have an additive influence on insulin sensitivity to adipocyte-derived TNF-alpha. Here, we hypothesized that 1) TNF-alpha produced by the adipose tissues of obese patients acts as a risk factor for periodontal inflammation, and 2) TNF-alpha produced due to periodontal inflammation may be an additional important factor influencing insulin sensitivity in both obese and type 2 diabetic patients. We believe that this interaction is a possible mechanism accounting for a 2-way relationship between type 2 diabetes and periodontal disease.

Background and aims: A characteristic feature of Crohn's disease (CD) is mesenteric adipose tissue hypertrophy. Mesenteric adipocytes or specific proteins secreted by them may play a role in the pathogenesis of CD. We recently identified adiponectin as an adipocyte specific protein with antiinflammatory properties. Here we report on expression of adiponectin in mesenteric adipose tissue of CD patients. Methods and results: Mesenteric adipose tissue specimens were obtained from patients with CD (n = 22), ulcerative colitis (UC) (n = 8) and, for controls, colon carcinoma patients (n = 28) who underwent intestinal resection. Adiponectin concentrations were determined by enzyme linked immunosorbent assay, and adiponectin mRNA levels were determined by real time quantitative reverse transcription-polymerase chain reaction. Tissue concentrations and release of adiponectin were significantly increased in hypertrophied mesenteric adipose tissue of CD patients compared with normal mesenteric adipose tissue of CD patients (p = 0.002, p = 0.040, respectively), UC patients (p = 0.002, p = 0.003), and controls (p,0.0001, p,0.0001). Adiponectin mRNA levels were significantly higher in hypertrophied mesenteric adipose tissue of CD patients than in paired normal mesenteric adipose tissue from the same subjects (p = 0.024). Adiponectin concentrations in hypertrophied mesenteric adipose tissue of CD patients with an internal fistula were significantly lower than those of CD patients without an internal fistula (p = 0.003). Conclusions: Our results suggest that adipocytes in hypertrophied mesenteric adipose tissue produce and secrete significant amounts of adiponectin, which could be involved in the regulation of intestinal inflammation associated with CD.

Since the frequency of subjects who carried at least one variant allele in TNF-alpha-1031, -863 or -857 SNPs was higher in periodontitis patients than in healthy subjects, TNF-alpha-1031, -863 and -857 SNPs appear to be associated with severe adult periodontitis in Japanese populations.

Periodontal treatment is effective in reducing CRP and TNF-alpha, while adiponectin does not appear to be influenced by periodontal treatment. Elevated levels of CRP and TNF-alpha may be associated with increased risk for future development of atherosclerosis in periodontitis patients.

This study was performed to investigate the aspects of interleukin‐6 (IL‐6) production in both the gingival tissue and the peripheral blood of patients with periodontal disease and of periodontally healthy subjects. In addition, IL‐6 expression in human gingival tissues was studied by reverse transcription‐polymerase chain reaction analysis and by immunoperoxidase staining with anti‐IL‐6 monoclonal antibody. The levels of IL‐6 in the culture supernatants from peripheral blood mononuclear cells (PBMC) stimulated with lipopolysaccharide and in serum were examined by bioassay. We detected IL‐6 mRNA expression in all inflamed gingival tissues (17/17) examined and in 2/4 in healthy gingival tissues. IL‐6 protein was detected mainly in endothelial cells, fibroblasts, and macrophages but not in the area containing T or B cells in the inflamed gingival tissues, and was not detected at all in healthy gingival tissues. There was no significant difference between the subjects with periodontal disease and those with healthy gingival tissues either in serum IL‐6 levels or in the amount of IL‐6 produced by PBMC. These results suggest that non‐lymphoid cells in inflamed gingival tissue may contribute to the pathogenesis of periodontal disease via IL‐6 production, and that the IL‐6 produced in gingival tissue may not reflect the IL‐6 levels in peripheral blood. J Periodontol 1994;65:147–153.

Efforts to understand the pathogenesis of periodontal diseases have been underway for decades. Studies of immunological aspects in addition to the structural components of gingival fibroblasts showed that the fibroblasts actively participate in immune and inflammatory events in periodontal diseases. Future strategies for the prevention and treatment of periodontal diseases should biologically regulate fibroblast activities. These cells are surrounded by monocyte-derived proinflammatory cytokines such as interleukin-1 beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and lymphocyte-derived interleukin-6 (IL-6) in inflamed gingival tissue. Recent anti-cytokine therapy for inflammatory diseases including rheumatoid arthritis aimed to inhibit the binding of cytokines to targeted cells such as fibroblasts and condrocytes. IL-1beta and TNF-alpha are thought to be therapeutic targets because these cytokines are essential for the initiation of inflammatory immune reactions and are produced for prolonged periods in inflammatory diseases. IL-6 is also a target, because it is abundantly present in inflammatory lesions and activates fibroblasts in the presence of soluble IL-6 receptor. In addition, these cytokines accelerate gingival fibroblasts to produce collagenolytic enzymes, resulting in tissue destruction. Soluble receptors for IL-1beta and TNF-alpha are suggested to be candidates for therapeutic molecules, but soluble receptor for IL-6 is suggested to be a factor-stimulating fibroblast. This paper will review the utilization of soluble receptors specific to inflammatory cytokines which potentially stimulate fibroblasts to regulate biological events involved in the pathogenesis of periodontal diseases.