Chemical sympathectomy inhibits periodontal disease in Fischer 344 rats.

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. Material and Methods: 6-OHDA (40-60 mu g/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 mu g/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 mu g/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.