title: The anti-inflammatory effects of sympathectomy in murine antigen-induced arthritis are associated with a reduction of Th1 and Th17 responses.
abstract: BACKGROUND
  Both facilitatory and inhibitory effects of the sympathetic nervous system (SNS) on experimental arthritis have been reported. It is unknown whether such bidirectional effects are inherent to all experimental arthritis models and/or whether critical time windows exist for influences of the SNS on inflammation.
  
  
  OBJECTIVE
  To assess the effect of sympathectomy at different time points on the course and severity of murine antigen-induced arthritis (AIA).
  
  
  METHODS
  AIA was induced in mice. Chemical sympathectomy with 6-hydroxydopamine was carried out either neonatally, in the immunisation phase, or immediately before AIA elicitation, or during the chronic phase. In sympathectomised and non-sympathectomised AIA mice the inflammatory process (joint swelling, histopathology of inflammation and joint destruction), pain-related behaviour and cellular and humoral immune responses were analysed.
  
  
  RESULTS
  Sympathectomy during AIA induction or neonatal sympathectomy significantly reduced the severity of acute AIA. Neither sympathectomy in the immunisation phase nor in the chronic phase influenced AIA. Flare-up reactions were reduced by sympathectomy just before flare-up or during the initial acute AIA stage. Sympathectomised AIA mice showed less hyperalgesia. Sympathectomy significantly reduced interleukin (IL) 2, IL-17 and transforming growth factor β in supernatants from lymph nodes and/or spleen cells and antigen-specific Th1-associated IgG2a in serum; IgG1 titres were unaffected. The ß blocker, propranolol, and the norepinephrine reuptake inhibitor bupropion produced similar anti-inflammatory effects, whereas the ß-adrenergic agonist isoproterenol increased AIA severity in neonatally sympathectomised mice.
  
  
  CONCLUSIONS
  Sympathetic activity mainly increases the severity of acute episodes of immune-mediated arthritis. Therapeutic reduction of sympathetic activity at acute stages attenuates inflammation, hyperalgesia and proinflammatory immune parameters.
authors.affiliation: Institute of Pathology, University Hospital, Friedrich Schiller University, Jena, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Ebbinghaus
authors.forename: Mieczyslaw
authors.initials: M
authors.lastname: Gajda
authors.forename: Michael K
authors.initials: MK
authors.lastname: Boettger
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Schaible
authors.forename: Rolf
authors.initials: R
authors.lastname: Bräuer
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D016207:Cytokines / Q000096:biosynthesis; D006930:Hyperalgesia / Q000517:prevention & control; D007074:Immunoglobulin G / Q000097:blood; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009638:Norepinephrine / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013154:Spleen / Q000276:immunology; D013563:Sympathectomy, Chemical / Q000379:methods*; D013564:Sympathetic Nervous System / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D016207:Cytokines; D007074:Immunoglobulin G; D009638:Norepinephrine