Enhancing central noradrenergic tone promotes IL-10 production and signalling in the CNS via ß-adrenoceptor activation (Abstract No. 20)

Eoin N. McNamee, Rodrigo Esteban Gonzalez Reyes, Andrew Harkin, Thomas J. Connor

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Abstract

Evidence suggests that the monoamine neurotransmitter noradrenaline elicits antiinflammatory actions in the central nervous system (CNS), and consequently may play an endogenous neuroprotective role in CNS disorders where inflammatory events contribute to pathology. Here we examined the possibility that enhancing central noradrenergic tone would induce expression of the anti inflammatory and neuroprotective cytokine IL-10 in rat brain. Administration of the noradrenaline reuptake inhibitor reboxetine (15 mg/kg; ip) in combination with the α2-adrenoceptor antagonist idazoxan (1 mg/kg; ip) was used as a pharmacological strategy to increase central noradrenaline availability. Our results demonstrate that the reboxetine+idazoxan combination induced IL-10 mRNA expression in both the cortex and hippocampus, and this was accompanied by an increase in IL-10 protein expression. In addition, reboxetine+idazoxan induced IL-10 signalling indicated by increased STAT3 phosphorylation and SOCS-3 mRNA expression. The ability of the drug combination to induce IL-10 production and signalling was mediated by ß-adrenoceptor activation, as all of the aforementioned effects were blocked by the ß-adrenoceptor antagonist propranolol. In addition, direct stimulation of central ß2-adrenoceptors with clenbuterol induced IL-10 production and signalling. In all, these data indicate that increasing central noradrenergic tone promotes an anti-inflammatory environment in the CNS, which may protect against neurodegeneration that occurs secondary to inflammation.
Original languageEnglish (US)
Pages163
Number of pages1
DOIs
StatePublished - Jul 15 2008
EventInternational Neuroimmunology Symposium - University College Dublin, Dublin, Ireland
Duration: Mar 13 2008Mar 14 2008

Conference

ConferenceInternational Neuroimmunology Symposium
Country/TerritoryIreland
CityDublin
Period3/13/083/14/08

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

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