Intact noradrenaline transporter is needed for the sympathetic fine-tuning of cytokine balance

Abstract

Earlier studies demonstrated that cytokine production is under the tonic control of noradrenaline. As the level and/or the duration of noradrenaline action is regulated by the noradrenaline transporter (NET), which is also a target of antidepressant treatment, we studied its role in the regulation of the cytokine response during inflammation. The endotoxin-evoked tumour necrosis factor-alpha (TNF-α) and interleukin-10 response was studied in genetically produced noradrenaline transporter-deficient (NET-KO) mice and by treatment with desipramine, a monoamine uptake-blocker antidepressant. NET-KO mice responded to endotoxin with significantly lower TNF-α and interleukin-10 production in comparison to their wild-type counterparts. Functional involvement of both α- and β-adrenoceptors could be demonstrated in our model systems, using 7,8-methylenedioxy-14α-hydroxy-alloberbane·HCl (CH-38083) and propranolol; however, the differences between the two phenotypes remained, suggesting a limited role of α-adrenoceptors in the observed changes. Acute treatment of both wild-type and NET-KO mice with desipramine significantly decreased the TNF-α response and significantly increased interleukin-10 production, indicating the role of an intact noradrenaline transporter in anti-inflammatory responses.