title: Sympathetic inhibition of IL-6, IFN-γ, and KC/CXCL1 and sympathetic stimulation of TGF-β in spleen of early arthritic mice.
abstract: OBJECTIVE
  The connection between sympathetic nerve fibers and immune cells in the spleen is known. In the context of arthritis, the functional meaning of the neuroimmune contact remains unclear. From immunization until disease outbreak, the sympathetic nervous system (SNS) has a proinflammatory influence which is converted into an anti-inflammatory influence after disease outbreak. This study investigated the influence of neuronally released neurotransmitters on IFN-γ, KC (CXCL1), IL-6, and TGF-β in spleen of mice shortly after outbreak of collagen type II-induced arthritis.
  
  
  METHODS
  Spleens were removed when animals reached an arthritis score of 3 on a scale of 1-16 (approx. on day 32) in order to generate 0.35 mm-thick spleen slices. Spleen slices were transferred to superfusion microchambers in order to electrically induce release of sympathetic neurotransmitters. By means of this technique, the effect of physiologically released neurotransmitters was investigated on secretion of IFN-γ, KC, IL-6, and TGF-β.
  
  
  RESULTS
  High amounts of IFN-γ, KC, IL-6, and TGF-β were released from superfused spleen, and electrical stimulation markedly inhibited IFN-γ, KC, and IL-6 release but pronouncedly stimulated TGF-β. The adrenergic influence via β-adrenoceptors stimulated release of IL-6 and, particularly, TGF-β. However, catecholamines inhibit release of IL-6 via α1-adrenergic pathways but without any effect on TGF-β. The co-transmitter adenosine stimulated IL-6 release via A1-adenosine receptors but no influence was recognized on TGF-β.
  
  
  CONCLUSIONS
  At disease outbreak, electrically released endogenous neurotransmitters of the SNS inhibit IFN-γ, KC, and IL-6 but β-adrenergically stimulate TGF-β. This creates an anti-inflammatory milieu that might be responsible for the observed dual influence of the SNS on arthritis.
authors.affiliation: Laboratory of Experimental Rheumatology and Neuroendocrine Immunology, Department of Internal Medicine I, University Hospital Regensburg, 93042 Regensburg, Germany. rainer.straub@klinik.uni-regensburg.de
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Straub
authors.forename: Luise
authors.initials: L
authors.lastname: Rauch
authors.forename: Lena
authors.initials: L
authors.lastname: Rauh
authors.forename: Georg
authors.initials: G
authors.lastname: Pongratz
mesh_terms: D058916:Adenosine A1 Receptor Antagonists / Q000494:pharmacology; D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000503:physiopathology*; D017776:Autonomic Pathways / Q000187:drug effects / Q000502:physiology; D054360:Chemokine CXCL1 / Q000032:analysis / Q000502:physiology*; D024043:Collagen Type II; D004558:Electric Stimulation; D005260:Female; D007371:Interferon-gamma / Q000032:analysis / Q000502:physiology*; D015850:Interleukin-6 / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D051379:Mice; D008811:Mice, Inbred DBA; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D054360:Chemokine CXCL1; D024043:Collagen Type II; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma