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The anti-inflammatory effects of sympathectomy in murine antigen-induced arthritis are associated with a reduction of Th1 and Th17 responses
  1. Matthias Ebbinghaus1,2,
  2. Mieczyslaw Gajda1,
  3. Michael K Boettger2,3,
  4. Hans-Georg Schaible2,
  5. Rolf Bräuer1
  1. 1Institute of Pathology, University Hospital, Friedrich Schiller University, Jena, Germany
  2. 2Institute of Physiology I, University Hospital, Friedrich Schiller University, Jena, Germany
  3. 3Present address: Bayer Schering Pharma AG, Wuppertal, Germany
  1. Correspondence to Professor Dr Rolf Bräuer, Institute of Pathology, University Hospital, Friedrich Schiller University, Ziegelmühlenweg 1, 07740 Jena, Germany; rolf.braeuer{at}med.uni-jena.de

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.

Objectives 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.

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Footnotes

  • Funding The authors thank the Government of Thuringia, the Interdisziplinäres Zentrum für klinische Forschung (IZKF) at the University of Jena, and Bundesministerium für Forschung und Technologie (BMBF, program “Immunopain”) for funding the position of Matthias Ebbinghaus.

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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