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

Eoin N. McNamee, Karen M. Ryan, Éadaoin W. Griffin, Rodrigo E. González-Reyes, Katie J. Ryan, Andrew Harkin, Thomas J. Connor

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)660-671
Number of pages12
JournalBrain, Behavior, and Immunity
Volume24
Issue number4
DOIs
StatePublished - May 2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience

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