Modulation of cytokine production by drugs with antiepileptic or mood stabilizer properties in anti-CD3- and anti-Cd40-stimulated blood in vitro.
Increased cytokine production possibly due to oxidative stress has repeatedly been shown to play a pivotal role in the pathophysiology of epilepsy and bipolar disorder. Recent in vitro and animal studies of valproic acid (VPA) report antioxidative and anti-inflammatory properties, and suppression of interleukin (IL)-6 and tumor necrosis factor (TNF)-α. We tested the effect of drugs with antiepileptic or mood stabilizer properties, namely, primidone (PRM), carbamazepine (CBZ), levetiracetam (LEV), lamotrigine (LTG), VPA, oxcarbazepine (OXC), topiramate (TPM), phenobarbital (PB), and lithium on the production of the following cytokines in vitro: interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-17, IL-22, and TNF-α. We performed a whole blood assay with stimulated blood of 14 healthy female subjects. Anti-human CD3 monoclonal antibody OKT3, combined with 5C3 antibody against CD40, was used as stimulant. We found a significant reduction of IL-1 and IL-2 levels with all tested drugs other than lithium in the CD3/5C3-stimulated blood; VPA led to a decrease in IL-1β, IL-2, IL-4, IL-6, IL-17, and TNF-α production, which substantiates and adds knowledge to current hypotheses on VPA's anti-inflammatory properties.
Department of Psychiatry, University of Leipzig, Semmelweisstr. 10, 04103 Leipzig, Germany.
Hubertus
0000-0003-1209-6073
H
Himmerich
Department of Psychiatry, University of Leipzig, Semmelweisstr. 10, 04103 Leipzig, Germany.
Stefanie
0000-0002-1369-8028
S
Bartsch
Epilepsy Center, Department of Neurology, University Hospital Erlangen, 91054 Erlangen, Germany.
Hajo
H
Hamer
Department of Psychiatry, University of Leipzig, Semmelweisstr. 10, 04103 Leipzig, Germany.
Roland
0000-0002-2829-6283
R
Mergl
Department of Psychiatry, University of Leipzig, Semmelweisstr. 10, 04103 Leipzig, Germany.
Jeremias
J
Schönherr
Department of Psychiatry, University of Leipzig, Semmelweisstr. 10, 04103 Leipzig, Germany.
Charlotte
C
Petersein
Department of Psychiatry, University of Leipzig, Semmelweisstr. 10, 04103 Leipzig, Germany.
Alexander
A
Munzer
Department of Psychiatry, University of Tasmania, Hobart, TAS 7001, Australia.
Kenneth Clifford
KC
Kirkby
Institute of Immunology, University of Leipzig, Johannisallee 30, 04103 Leipzig, Germany.
Katrin
K
Bauer
Institute of Immunology, University of Leipzig, Johannisallee 30, 04103 Leipzig, Germany.
Ulrich
U
Sack
D000328:Adult; D000339:Affect / Q000187:drug effects*; D000927:Anticonvulsants / Q000494:pharmacology*; D017252:CD3 Complex / Q000378:metabolism*; D019013:CD40 Antigens / Q000378:metabolism*; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000494:pharmacology; D055815:Young Adult
D000927:Anticonvulsants; D017252:CD3 Complex; D019013:CD40 Antigens; D016207:Cytokines; D016853:Muromonab-CD3