title: The sympathetic nervous system stimulates anti-inflammatory B cells in collagen-type II-induced arthritis.
abstract: BACKGROUND
  As previously shown, the sympathetic nervous system (SNS) shows proinflammatory activity during initiation of arthritis but is anti-inflammatory in established collagen-induced arthritis (CIA). Interleukin 10 (IL-10)-producing B cells suppress arthritis and are a potential target of the SNS because (1) B cells express functional β(2)-adrenoceptors (β(2)ARs) and (2) IL-10, at least in monocytes/macrophages, is regulated in a cAMP/PKA/CREB-dependent manner.
  
  
  OBJECTIVE
  To test the hypothesis that anti-inflammatory effects of the SNS in CIA are mediated by stimulating IL-10-producing anti-inflammatory B cells.
  
  
  METHODS
  Collagen-induced arthritis in DBA/1 mice, sympathectomy, adoptive B cell transfer, in vitro B cell culture, and assessment of B cell IL-10 production.
  
  
  CONCLUSIONS
  Mice treated with B cells from SNS-intact mice showed less severe arthritis than mice treated with B cells from sympathectomised mice. This anti-inflammatory action of B cells from SNS-intact mice correlated with increased IL-10 produced by B cells, which was mediated by norepinephrine (NE), in a β(2)AR, PKA-dependent manner. However, an NE-mediated increase in IL-10 was seen only in B cells from immunised but not naive mice, explaining in part the anti-inflammatory properties of the SNS in the late phase of arthritis. Finally, animals treated with B cells isolated from immunised mice and activated in vitro in the presence of a β(2)AR stimulus showed a decrease in arthritis severity in comparison with controls, an approach that might be used for future cellular treatment strategies.
authors.affiliation: Laboratory of Experimental Rheumatology and Neuroendocrine Immunology, Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany. georg.pongratz@klinik.uni-regensburg.de
authors.forename: Georg
authors.initials: G
authors.lastname: Pongratz
authors.forename: Madlen
authors.initials: M
authors.lastname: Melzer
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Straub
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D016753:Interleukin-10 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009638:Norepinephrine / Q000494:pharmacology; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology; D013154:Spleen / Q000276:immunology; D013562:Sympathectomy; D013564:Sympathetic Nervous System / Q000276:immunology*; D013566:Sympathomimetics / Q000494:pharmacology; D013726:Terbutaline / Q000494:pharmacology
chemical_list: D018343:Receptors, Adrenergic, beta-2; D013566:Sympathomimetics; D016753:Interleukin-10; D013726:Terbutaline; D009638:Norepinephrine