Peripheral kappa opioid receptors activation reduces alveolar bone loss in rats by modulating interleukin-6 and -10

Objective: The beneficial effects of kappa opioid agonist U-50,488 in preventing periodontal disease (PD) progression in rats have already been described, but its mechanism of action is unknown. The present study evaluated the expression of TNF-alpha, IL-6, IL-8 and IL-10 in the gingival tissues of rats with ligature-induced PD, treated with U-50,488. It also correlated the effects of this agonist with myeloperoxidase (MPO) activity and the presence of osteoclasts. Design: Male Holtzman rats weighing 250-300 g were divided into four groups: (1) control, (2) ligature, (3) ligature + saline and (4) ligature + kappa agonist. Experimental PD was induced by placing a sterile silk ligature around the 2nd left upper molar. Rats from groups 3 to 4 were locally administered with either saline or U-50,488, respectively, from day 3 to day 5 following ligation. After 5 or 11 days, the rats were euthanized and periodontal tissue samples were collected for histological and morphometric analysis and for determination of TNF-alpha, IL-6, IL-8, IL-10 and MPO. Results: Ligature placement induced significant alveolar bone loss. The number of osteoclasts, degree of MPO activity, IL-6, IL-8 and TNF-alpha expression were also increased by PD. U-50,488 reduced both bone loss and the number of osteoclasts, but did not alter histological inflammatory infiltrate or MPO activity. U-50,488 significantly reduced IL-6 and increased IL-10 levels, but did not affect TNF-alpha and IL-8. Conclusion: Lowering the levels of IL-6 and increasing IL-10 are important mechanisms by which U-50,488 reduces alveolar bone loss in ligature-induced periodontal disease. (C) 2010 Elsevier Ltd. All rights reserved.