title: Neuronally released sympathetic neurotransmitters stimulate splenic interferon-gamma secretion from T cells in early type II collagen-induced arthritis.
abstract: OBJECTIVE
  The sympathetic nervous system confers a proinflammatory effect during the early phase of type II collagen-induced arthritis (CIA). These effects might be mediated by up-regulation of cytokines such as interferon-gamma (IFNgamma) or chemokines such as CXCL1 (cytokine-induced neutrophil chemoattractant, or KC). This study aimed to identify the role of sympathetic neurotransmitters in splenic secretion of IFNgamma and KC shortly after the onset of CIA.
  
  
  METHODS
  At different time points during CIA, we determined the density of sympathetic nerve fibers in the spleens of mice. Spleens were removed when the mouse joints were assessed an arthritis score of 3 (at approximately day 32). Spleen slices (0.35 mm thick) were transferred to superfusion microchambers to allow observation of the effects of physiologically released sympathetic neurotransmitters on secretion of IFNgamma and KC.
  
  
  RESULTS
  Compared with control mice, mice with CIA demonstrated a decrease in sympathetic nerve fiber density in the spleens, which reached a minimum density shortly after the start of symptomatic arthritis (day 32). T cell depletion markedly reduced splenic secretion of IFNgamma and KC. Electrical-field stimulation of the spleen slices reduced the secretion of IFNgamma, which was attenuated by an alpha1-adrenergic antagonist. In addition, splenic IFNgamma secretion was stimulated by norepinephrine, via beta-adrenergic receptors, and adenosine, via A1 adenosine receptors. Similarly, splenic KC secretion was stimulated by norepinephrine, via beta-adrenergic receptors.
  
  
  CONCLUSIONS
  The results of this study demonstrate a reduction of sympathetic nerve fibers in the spleens of arthritic animals. Nevertheless, sympathetic nerves help to increase secretion of IFNgamma and KC, which, at the early stages shortly after the onset of CIA, can contribute to the proinflammatory effect of the sympathetic nervous system.
authors.affiliation: University Hospital Regensburg, 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: Alexander
authors.initials: A
authors.lastname: Fassold
authors.forename: Torsten
authors.initials: T
authors.lastname: Lowin
authors.forename: Georg
authors.initials: G
authors.lastname: Pongratz
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001169:Arthritis, Experimental / Q000503:physiopathology*; D018925:Chemokines / Q000378:metabolism*; D024043:Collagen Type II; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism*; D051379:Mice; D008811:Mice, Inbred DBA; D018377:Neurotransmitter Agents / Q000378:metabolism* / Q000502:physiology*; D010665:Phenylpropanolamine / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000502:physiology; D013154:Spleen / Q000294:innervation / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D018925:Chemokines; D024043:Collagen Type II; D018377:Neurotransmitter Agents; D011941:Receptors, Adrenergic; D010665:Phenylpropanolamine; D007371:Interferon-gamma; D000241:Adenosine