Noradrenaline acting at central β-adrenoceptors induces interleukin-10 and suppressor of cytokine signaling-3 expression in rat brain: Implications for neurodegeneration Academic Article


  • Brain, Behavior, and Immunity


  • Evidence indicates that the monoamine neurotransmitter noradrenaline elicits anti-inflammatory actions in the central nervous system (CNS), and consequently may play a neuroprotective role where inflammatory events contribute to CNS pathology. Here we examined the ability of pharmacologically enhancing central noradrenergic tone to induce expression of anti-inflammatory cytokines in rat brain. Administration of the noradrenaline reuptake inhibitor reboxetine (15mg/kg; ip) combined with the α2-adrenoceptor antagonist idazoxan (1mg/kg; ip) induced interleukin-10 (IL-10) expression in rat cortex and hippocampus. In addition, these drug treatments induced IL-10 signaling as indicated by increased STAT3 phosphorylation and suppressor of cytokine signaling-3 (SOCS-3) mRNA expression. In contrast to the profound increase in IL-10 induced by the reboxetine/idazoxan combination, the other two broad spectrum anti-inflammatory cytokines IL-4 and TGF-β were not induced by this treatment. The ability of combined treatment with reboxetine and idazoxan to induce IL-10 and SOCS3 expression was mediated by β-adrenoceptor activation, as their induction was blocked by pre-treatment with the β-adrenoceptor antagonist propranolol. Moreover, administration of the brain penetrant β2-adrenoceptor agonist clenbuterol induced a time- and dose-dependent increase in central IL-10 and SOCS3 expression, and the ability of clenbuterol to induce IL-10 and SOCS-3 expression was blocked by the centrally acting β-adrenoceptor antagonist, propranolol, and was mimicked by the highly selective β2-adrenoceptor agonist formoterol. In all, these data indicate that increasing central noradrenergic tone induces IL-10 production and signaling in the CNS, which may protect against neurodegeneration.

publication date

  • 2010-5-1


  • 24


  • Adrenergic Receptors
  • Anti-Inflammatory Agents
  • Brain
  • Central Nervous System
  • Clenbuterol
  • Cytokines
  • Formoterol Fumarate
  • Hippocampus
  • Idazoxan
  • Interleukin-10
  • Interleukin-4
  • Messenger RNA
  • Neurotransmitter Agents
  • Norepinephrine
  • Pathology
  • Pharmaceutical Preparations
  • Phosphorylation
  • Propranolol
  • Reboxetine

International Standard Serial Number (ISSN)

  • 0889-1591

number of pages

  • 12

start page

  • 660

end page

  • 671