Neonatal dexamethasone and chronic tianeptine treatment inhibit ligature-induced periodontitis in adult rats

Objective: The responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis has been found to play a significant role for susceptibility and resistance to periodontal disease. In the present study we have investigated the effects of two different treatment strategies, which have been found to down-regulate the HPA axis, on ligature-induced periodontitis. Methods: In experiment 1, newborn rats were treated with the synthetic glucocorticoid hormone dexamethasone-21-phosphate, which permanently down-regulates HPA axis responsiveness. In experiment 2, adult rats were treated with the novel antidepressant drug tianeptine, which opposes the action of stress. Periodontitis was inflicted upon all rats. Just before decapitation the animals received gram-negative bacterial lipopolysaccharide (LPS) to induce a robust immune and HPA axis response. Results: Compared to the saline-treated control rats, dexamethasone-treated rats had significantly less periodontal bone loss (p < 0.01), reduced expression of glucocorticoid receptors in the hippocampus (p < 0.001), lower corticosterone (p = 0.01) and higher plasma levels of the cytokine tumor necrosis factor (TNF)-alpha (p < 0.05) after LPS challenge. Also the tianeptine-treated rats showed significantly reduced periodontal bone loss (p = 0.01), enhanced plasma levels of TNF-alpha (p < 0.05), and transforming growth factor-1 beta (p < 0.01), whereas no significant difference was found in corticosterone levels. Conclusion: An individual's responsiveness to danger signals, whether they are of immunological, chemical, or psychological origin, may be an important factor for explaining variability in susceptibility to periodontal disease. The results may provide new insight into the mechanisms of periodontal disease development, and open new vistas for disease prevention.