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Effect of valproate on plasma levels of interleukin-6 in healthy male humans

Shiah, I-Shina; Yatham, Lakshmi N.b; Yeh, Chin-Bina; Ravindran, Arun V.c

International Clinical Psychopharmacology: November 2005 - Volume 20 - Issue 6 - p 295-298

Valproate exerts many biochemical and physiological effects and may have a modulating effect on the immune system. The present study aimed to determine whether there is a treatment effect of valproate on plasma levels of the pro-inflammatory cytokine, interleukin (IL)-6, in healthy male humans. Plasma levels of IL-6 were measured in 10 healthy male humans before and after 7 days of treatment with 1000 mg per day of valproate (i.e. 500 mg in the morning and 500 mg in the evening). All the healthy subjects had no past or current psychiatric disorder. They reported to the outpatient clinic at 09.00 h for baseline sampling. Subsequently, they were commenced on valproate 1000 mg per day for 7 days. They took the last dose of valproate at 22.00 h on the day 7, and post-treatment blood sampling for plasma levels of IL-6 was carried out on day 8. An additional blood sample was also taken from each subject at the same time to measure plasma levels of valproic acid for drug compliance. We found a significant increase in plasma levels of IL-6 after the 7 days of valproate treatment in healthy male subjects. Furthermore, there was a significant positive correlation between the changes in plasma IL-6 and blood levels of valproic acid. The findings of this study are consistent with previous studies on subjects with epilepsy, suggesting a modulating effect of valproate on the pro-inflammatory cytokine IL-6 in humans. However, studies with a larger number of participants and employing a double-blind, placebo-control group are required to confirm the findings, and also the levels of other cytokines should be measured to generalize the effect to the immune system.

aDepartment of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

bDivision of Mood Disorders, Department of Psychiatry, The University of British Columbia, Vancouver, BC, Canada

cMood and Anxiety Program, Center for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada

Correspondence and requests for reprints to I- Shin Shiah, Department of Psychiatry, Tri-Service General Hospital, No. 325, Cheng-Kung Road, Sec. 2, Nei-Hu District, Taipei, 114, Taiwan

Tel: +011 886 2 8792 7431; fax: +011 886 2 8791 2161;


Received 8 March 2005 Accepted 14 June 2005

© 2005 Lippincott Williams & Wilkins, Inc.