title: Chemical sympathectomy inhibits periodontal disease in Fischer 344 rats.
abstract: OBJECTIVE
  The responsiveness of the sympathetic nervous system (SNS) and the hypothalamic--pituitary--adrenal (HPA) axis plays a major role in immune regulation and for the outcome of infections and inflammatory disorders. This study was designed to investigate whether chemical SNS denervation with the noradrenaline-selective neurotoxic drug 6-hydroxydopamine (6-OHDA), which destroys peripheral noradrenaline terminals, would influence immune responses to Gram-negative bacterial lipopolysaccharide (LPS) stimulation, and the progression of ligature-induced periodontal disease in Fischer 344 rats.
  
  
  METHODS
  6-OHDA (40--60 microg/kg) or vehicle was injected intraperitoneally (i.p.) on days 1, 3 and 5, 10 days before application of the ligatures, and thereafter weekly in doses of 80 microg/kg. Periodontal disease was assessed when the ligatures had been in place for 49 days. At 24 and 2 h before decapitation, all rats received LPS (150 microg/kg i.p.) to induce a robust immune and HPA axis response.
  
  
  RESULTS
  The 6-OHDA-treated rats showed significantly reduced bone loss as measured by digital X-rays (p< 0.01), and enhanced levels of the cytokines transforming growth factor-beta (p=0.05) and interleukin-6 (p=0.05), as well as the HPA axis derived hormone corticosterone (p=0.01), induced by LPS stimulation.
  
  
  CONCLUSIONS
  6-OHDA-induced chemical sympathectomy inhibits ligature-induced periodontal disease in this model. This effect may be attributable to the well-documented ability of the SNS to regulate immune system function primarily via the adrenergic neurotransmitter noradrenaline released at sympathetic nerve terminals. The enhanced HPA axis activation may be a compensatory response that reduces the T helper (Th)2 to Th1 skewing effect of treatment with 6-OHDA.
authors.affiliation: Department of Periodontology, Faculty of Dentistry, University of Oslo, Oslo, Norway. tbreivik@odont.uio.no
authors.forename: Torbjørn
authors.initials: T
authors.lastname: Breivik
authors.forename: Yngvar
authors.initials: Y
authors.lastname: Gundersen
authors.forename: Per Kristian
authors.initials: PK
authors.lastname: Opstad
authors.forename: Frode
authors.initials: F
authors.lastname: Fonnum
mesh_terms: D016301:Alveolar Bone Loss / Q000517:prevention & control*; D000818:Animals; D003345:Corticosterone / Q000096:biosynthesis; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D007274:Injections, Intraperitoneal; D016753:Interleukin-10 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides; D008297:Male; D016627:Oxidopamine / Q000008:administration & dosage; D010510:Periodontal Diseases / Q000209:etiology / Q000276:immunology* / Q000378:metabolism*; D010913:Pituitary-Adrenal System / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D018709:Statistics, Nonparametric; D013315:Stress, Psychological / Q000150:complications / Q000276:immunology; D013563:Sympathectomy, Chemical / Q000379:methods*; D013565:Sympatholytics / Q000008:administration & dosage; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D013565:Sympatholytics; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D016627:Oxidopamine; D003345:Corticosterone