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Impact of mood stabilizers and antiepileptic drugs on cytokine production in-vitro


Himmerich, H and Bartsch, S and Hamer, H and Mergl, R and Schonherr, J and Petersein, C and Munzer, A and Kirkby, KC and Bauer, K and Sack, U, Impact of mood stabilizers and antiepileptic drugs on cytokine production in-vitro, Journal of Psychiatric Research, 47, (11) pp. 1751-1759. ISSN 0022-3956 (2013) [Refereed Article]

Copyright Statement

Copyright 2013 Elsevier Ltd

DOI: doi:10.1016/j.jpsychires.2013.07.026


Changes within the immune system have been reported to contribute to the pathophysiology of bipolar disorder and epilepsy. Interestingly, overlapping results regarding the cytokine system have been found for both diseases, namely alterations of interleukins IL-1β, IL-2, IL-4, IL-6, and tumor necrosis factor-α (TNF-α). However, the effect of mood stabilizers and antiepileptic drugs (AEDs) on these cytokines has not been systematically evaluated, and their effect on IL-17 and IL-22, other immunologically important cytokines, has not been reported. Therefore, we systematically measured levels of IL-1β, IL-2, IL-4, IL-6, IL-17, IL-22 and TNF-α in stimulated blood of 14 healthy female subjects in a whole blood assay using the toxic shock syndrome toxin TSST-1 as stimulant. Blood was supplemented with the mood stabilizers or antiepileptic drugs primidone (PRM), carbamazepine (CBZ), levetiracetam (LEV), lamotrigine (LTG), valproic acid (VPA), oxcarbazepine (OXC), topiramate (TPM), phenobarbital (PB), lithium, or no drug. IL-1β production was significantly decreased by PRM, CBZ, LEV, LTG, OXC, PB and lithium. IL-2 significantly decreased by PRM, CBZ, LEV, LTG, VPA, OXC, TPM and PB. IL-22 significantly increased by PRM, CBZ, LEV, OXC, TPM and lithium and decreased by VPA. TNF-α production significantly decreased under all applied drugs. The mechanism of action and side effects of mood stabilizers and AEDs may involve modulation of IL-1β, IL-2, IL-22 and TNF-α signaling pathways. IL-22 may be a research target for specific therapeutic effects of mood stabilizers and AEDs. These drugs might influence cytokine production by modulating ion channels and γ-aminobutyric acid (GABA) receptors of immune cells.

Item Details

Item Type:Refereed Article
Keywords:cytokines, bipolar disorder, epilepsy, mood stabilizer, antiepileptic drugs
Research Division:Health Sciences
Research Group:Health services and systems
Research Field:Mental health services
Objective Division:Health
Objective Group:Public health (excl. specific population health)
Objective Field:Mental health
UTAS Author:Kirkby, KC (Professor Kenneth Kirkby)
ID Code:87285
Year Published:2013
Web of Science® Times Cited:68
Deposited By:Medicine
Deposited On:2013-11-12
Last Modified:2014-05-14

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