Intact noradrenaline transporter is needed for the sympathetic fine-tuning of cytokine balance.
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.
Selmeczy
Zsolt
Z
Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences P.O.B. 67, H-1450 Budapest, Hungary.
Szelényi
Judit
J
Vizi
E Sylvester
ES
D000320:Adrenergic Fibers / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001599:Berberine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D050484:Norepinephrine Plasma Membrane Transport Proteins; D011433:Propranolol / Q000494:pharmacology; D027981:Symporters / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D050484:Norepinephrine Plasma Membrane Transport Proteins; C493228:Slc6a2 protein, mouse; D027981:Symporters; D014409:Tumor Necrosis Factor-alpha; D001599:Berberine; C048886:7,8-(methylenedioxy)-14-hydroxyberbane; D016753:Interleukin-10; D011433:Propranolol