title: Chronic treatment with the glucocorticoid receptor antagonist RU486 inhibits diabetes-induced enhancement of experimental periodontitis.
abstract: OBJECTIVE
  Chronic hypothalamic-pituitary-adrenal (HPA) axis hyperactivity and excessive glucocorticoid hormone release have been associated with diabetes, altered immune responses and increased susceptibility to periodontitis. In the present study we tested the impact of streptozotocin (STZ)-induced diabetes on ligature-induced periodontitis and the effect of subsequent treatment with the glucocorticoid receptor (GR) antagonist, RU486.
  
  
  METHODS
  A single dose of STZ [45 mg/kg, intraperitoneally (i.p.)] or vehicle was given 10 d before induction of ligature-induced periodontitis and implantation subcutaneously of a drug pellet containing the GR antagonist, RU486, or a placebo pellet. Periodontitis was assessed when the ligatures had been in place for 21 d. Two hours before decapitation all rats received gram-negative bacterial lipopolysaccharide (LPS) (150 μg/kg, i.p.) to induce a robust immune and stress response.
  
  
  RESULTS
  Compared with control rats, STZ-treated rats developed significantly more periodontal bone loss, and RU486 treatment of STZ -treated rats significantly inhibited this effect. STZ-treated rats also showed significantly higher levels of the HPA axis-derived hormone, corticosterone, as well as of the proinflammatory cytokine, tumor necrosis factor-alpha (TNF-α), but lower levels of the anti-inflammatory cytokines interleukin-10 (IL-10) and transforming growth factor-1beta (TGF-1β) after LPS stimulation. GR blockade had no statistically significant effects on these measurements in diabetic rats, but tended to enhance the levels of TNF-α and TGF-1β, and reduce the levels of IL-10 and blood glucose.
  
  
  CONCLUSIONS
  In diabetic subjects, excessive GR activation as a result of chronic high levels of glucocorticoid hormones may alter immune-system responses in a manner that may increase the susceptibility to periodontitis.
authors.affiliation: Faculty of Dentistry, Department of Periodontology, University of Oslo, Oslo, Norway; Division of Protection, Norwegian Defence Research Establishment, Kjeller, Norway.
authors.forename: T
authors.initials: T
authors.lastname: Breivik
authors.forename: Y
authors.initials: Y
authors.lastname: Gundersen
authors.forename: P
authors.initials: P
authors.lastname: Gjermo
authors.forename: P-K
authors.initials: PK
authors.lastname: Opstad
mesh_terms: D016301:Alveolar Bone Loss / Q000000981:diagnostic imaging / Q000517:prevention & control; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D003345:Corticosterone / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications*; D004343:Drug Implants; D004926:Escherichia coli / Q000276:immunology; D006727:Hormone Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D016753:Interleukin-10 / Q000097:blood; D008070:Lipopolysaccharides / Q000276:immunology; D015735:Mifepristone / Q000008:administration & dosage / Q000627:therapeutic use*; D010518:Periodontitis / Q000517:prevention & control*; D010913:Pituitary-Adrenal System / Q000187:drug effects; D010919:Placebos; D011859:Radiography; D011897:Random Allocation; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors*; D013311:Streptozocin; D053773:Transforming Growth Factor beta1 / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D001786:Blood Glucose; D004343:Drug Implants; D006727:Hormone Antagonists; D008070:Lipopolysaccharides; D010919:Placebos; D011965:Receptors, Glucocorticoid; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015735:Mifepristone; D013311:Streptozocin; D003345:Corticosterone
keywords: brain-neuroendocrine-immune interactions; cytokines; diabetes; lipopolysaccharides; periodontitis; rats