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A8.16 The cholinergic anti-inflammatory pathway does not influence sialadenitis or diabetes in the non-obese diabetic mouse model of SjÖgren’s syndrome
  1. FA Koopman1,
  2. N Roescher1,
  3. JL Vosters1,
  4. N Broekstra2,
  5. PP Tak1,3,4,
  6. MJ Vervoordeldonk1,2
  1. 1 Department of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
  2. 2 Arthrogen BV, Amsterdam, The Netherlands
  3. 3 University of Cambridge, Cambridge, UK
  4. 4 GlaxoSmithKline, Stevenage, UK

Abstract

Introduction Activation of the cholinergic anti-inflammatory (CAP) reduces inflammation in different animal models, while abrogation of the pathway has been shown to increase inflammation. Sjögren’s syndrome (SjS) is a chronic autoimmune disease of the salivary glands, which can currently only be treated symptomatically. The pathogenesis of SjS can be studied in the non-obese diabetic (NOD) mouse model; these mice spontaneously develop immune cell infiltration in the salivary glands (SG) in addition to type I diabetes due to pancreatic immune cell infiltration (insulitis).

Methods The CAP was activated in the NOD mouse model for 4 weeks (10–14 weeks of age) with two agonists of the α7 subunit of nicotinic acetylcholine receptor (α7nAChR), AR-R17779 and nicotine. In the next study the pathway was abrogated by unilateral cervical vagotomy performed at 12 weeks of age; animals were monitored until 20 weeks of age. Alpha-7nAChR expression and focus score (FS) were evaluated in the SG in addition to the insulitis score in the pancreas. Salivary function was evaluated by measuring stimulated salivary flow. Cytokines levels were measured in serum and SG.

Results Alpha-7nAChR was expressed on myoepithelial cells in the SG surrounding the ducts. There were no changes in cytokine production in the serum, but in the SG monocyte chemotactic protein (MCP)-1 was reduced after AR-R17779 treatment (p = 0.023) and tumour necrosis factor (TNF) production was increased in the vagotomy group (p = 0.042). This however did not change the FS or stimulated salivary flow in the two CAP intervention studies. The NOD mice developed diabetes more rapidly in the vagotomy group, but at completion of the study the same number of animals had developed diabetes and there were no significant differences in insulitis scores.

Conclusion The cholinergic anti-inflammatory pathway does not influence the inflammatory processes in the NOD mouse model of SjS and type I diabetes.

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