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-alpha) 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-alpha and interleukin-10 production in comparison to their wild-type counterparts. Functional involvement of both alpha- and beta-adrenoceptors could be demonstrated in our model systems, using 7,8-methylenedioxy-14 alpha-hydroxy-alloberbane.HCl (CH-38083) and propranolol; however, the differences between the two phenotypes remained, suggesting a limited role of alpha-adrenoceptors in the observed changes. Acute treatment of both wild-type and NET-KO mice with desipramine significantly decreased the TNF-alpha response and significantly increased interleukin-10 production, indicating the role of an intact noradrenaline transporter in anti-inflammatory responses.

journal_name

Eur J Pharmacol

authors

Selmeczy Z,Szelényi J,Vizi ES

doi

10.1016/s0014-2999(03)01721-7

keywords:

subject

Has Abstract

pub_date

2003-05-23 00:00:00

pages

175-81

issue

1-3

eissn

0014-2999

issn

1879-0712

pii

S0014299903017217

journal_volume

469

pub_type

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