Glucocorticoid receptor antagonist RU 486 treatment reduces periodontitis in Fischer 344 rats.
Inappropriate hypothalamic pituitary adrenal (HPA) axis regulation of immune responses to bacterial challenges has been found to play an important role in infections and inflammatory disease susceptibility and progression. In the present study we investigated the tissue effects of experimental periodontitis in Fischer 344 rats, which were subcutaneously (s.c.) injected with 20 mg/kg of the glucocorticoid receptor antagonist and active antiglucocorticoid agent RU 486 every second day over a period of 14 d. Periodontitis was induced by placing a bacterial plaque retentive silk ligature in the gingival sulcus around the neck of maxillary right 2nd molar teeth 1 d after the first injection in 10 RU 486-treated and 10 vehicle (1,2-propanediol)-treated control animals. The contralateral maxillary left 2nd molars served as internal control teeth for naturally occurring periodontitis. Disease progression was evaluated radiographically and histometrically. The average level of corticosterone in blood at sacrifice was significantly lower in the RU 486-treated animals as compared to controls. The experimental animals also developed significantly less periodontal breakdown at both experimental and control teeth compared to the vehicle-treated control animals. The results support our recent findings showing that HPA hyper-reactivity, either genetically determined or experimentally induced, stimulates periodontal disease susceptibility. These findings suggest that central nervous regulation of inflammatory responses to dental plaque microorganisms in the gums may modulate periodontal disease susceptibility and progression.
Breivik
T
T
Department of Periodontology, Faculty of Dentistry, University of Oslo, Norway. tbreivik@odont.uio.no
Thrane
P S
PS
Gjermo
P
P
Opstad
P K
PK
D000818:Animals; D004195:Disease Models, Animal; D005938:Glucocorticoids / Q000037:antagonists & inhibitors; D006727:Hormone Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D008297:Male; D015735:Mifepristone / Q000494:pharmacology / Q000627:therapeutic use*; D015213:Neuroimmunomodulation / Q000187:drug effects; D010518:Periodontitis / Q000188:drug therapy* / Q000503:physiopathology; D010913:Pituitary-Adrenal System / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344
D005938:Glucocorticoids; D006727:Hormone Antagonists; D015735:Mifepristone