Study of TNF-α, IL-1βand LPS Levels in the Gingival Crevicular Fluid of a Rat Model of Diabetes Mellitus and Periodontitis

Abstract

OBJECTIVE: In this study, we sought to investigate the dynamic changes in the levels of TNF-α, IL-1β and LPS in the gingival crevicular fluid (GCF) in a rat model of diabetes mellitus (DM) and periodontitis (PD). Additionally, we evaluated alveolar bone loss and the histopathological response associated with experimental diabetes mellitus and experimental periodontitis.METHODS: DM and PD were induced together in 15 rats (group 1) by streptozotocin injection and ligature induction. Periodontitis alone was produced by ligature induction in 15 rats (group 2), diabetes alone was produced by streptozotocin injection in 15 rats (group 3), and fifteen systemically and periodontally healthy rats were used as controls (group 4). The gingival TNF-α, IL-1β and LPS levels were measured by using ELISA method. Periodontal destruction was assessed by measuring the alveolar bone loss. Periodontal inflammation was quantified by histopathological grading in H&E stained samples.RESULTS: Higher levels of TNF-α, IL1-β and LPS, increased alveolar bone loss and more serve histopathology were found in group 1 compared with group 2, group 3 and group 4 (p < 0.05). The quantities of TNF-α, IL1-β and LPS, the amount of alveolar bone loss and the severity of the histopathological finding were greater in group 2 than group 3 and group 4 (p < 0.05). Group 3 demonstrated higher levels of TNF-α, IL1-β and LPS, increased alveolar bone loss and more serve histopathology than group 4 (p < 0.05). Statistically significant differences were noted between all of the groups.CONCLUSIONS: These data indicate that DM may lead to enhanced TNF-α, IL1-β and LPS production in the periodontal tissues. The resorption values of alveolar bone and the histological inflammation were more severe in rats with periodontitis and diabetes mellitus than in those with periodontitis alone, diabetes mellitus alone and control rats. Our findings are consistent with the hypothesis that hyperglycemia contributes to the heightened inflammatory response associated with periodontitis.

The Role of Osteoimmunology in Periodontal Disease

“…In addition to the leukocytes of the inflammatory infiltrate, the cells residing in the normal periodontium, including fibroblasts, junctional epithelial cells, and vascular endothelium (all of which function in the healthy periodontium to maintain homeostasis), can be hijacked by exposure to bacterial agents such as lipopolysaccharide (LPS), cytokines such as interleukin-1 (IL-1) or tumor necrosis factor- α (TNF- α ), or prostaglandins such as prostaglandin E2 (PGE-2) and become major participants in tissue destruction [8, 16, 17]. …”

“…In patients with periodontal disease, IL-1 β expression was elevated in the GCF at sites of recent bone and attachment loss [17, 67, 68]. IL-1 β was also found to be higher in diseased periodontal tissue samples compared to tissue samples from healthy individuals, and the level of expression correlates highly with clinical parameters [64, 69].…”

“…In patients with periodontal disease, TNF- α expression was elevated in the GCF at sites where bone and attachment loss have just occurred [17, 67, 68, 82, 83]. It was also found to be higher in diseased periodontal tissue samples compared to tissue samples from healthy individuals [69].…”

Short‐Term Effects of Non‐Surgical Periodontal Treatment on the Gingival Crevicular Fluid Cytokine Profiles in Sites With Induced Periodontal Defects: A Study on Dogs With and Without Streptozotocin‐Induced Diabetes

“…Increased expression of such proinflammatory cytokines in the GCF has been associated with the production of reactive oxygen species (ROS) produced as a result of oxidative stress under periodontal inflammatory conditions 16 . In addition, an increased formation and accumulation of advanced glycation end products (AGEs) in the periodontal tissues under hyperglycemia has also been proposed to increase the burden of proinflammatory cytokines in the serum and GCF 17,18 . In this context, analysis of proinflammatory cytokines in GCF provides valuable information regarding the pathophysiologic processes associated with periodontitis.…”

Effects on Alveolar Bone of Diabetes Mellitus Induced by Streptozotocin in Rats. Histopathologic and Immunohistochemical Study

“…In a research C57BL Db/db mice that developed diabetes at six to eight weeks of age to study decreased osteoclastogenesis in bacteria-stimulated bone loss (He et al, 2004). Jiang et al (2013) reported resorption values of alveolar bone in the upper second molar of four groups of rats at different time points. The rats with periodontal disease (PD) and diabetes mellitus (DM) showed more alveolar bone loss than those with PD alone, DM alone, and control rats at the same time point.…”