Valproic acids inhibits interleukin-1-induced expression of cyclooxigenase-2 and prostaglandin release in human neuroblastoma cells

The mechanisms of action of mood stabilising agents have not been fully elucidated so far. Recent data have suggested that mood stabilisers such as lithium or valproic acid may interfere with phospholipase A2 activity and synthesis of prostaglandines (PG). Here we investigated whether valproic acid is able to inhibit interleukin-1-(IL-1-)induced expression of cyclooxigenase-2 (COX-2) and synthesis of PGE2 in the human neuroblastoma cell line SH-N-SK. Valproic acid dose dependently inhibited IL-1-induced COX-2 expression and protein synthesis as well as PGE2 release. Valproic acid did not inhibit enzymatic activity of COX-2. Further work is currently ongoing to elucidate the underlying molecular mechanism of this inhibition. Our data support the hypothesis that modulation of cyclooxigenase and PG synthesis may be an interesting mechanism of the action of mood stabilising agents and that non-steroidal antiinflammatory agents (COX-2 inhibitors) might be potential substances for the treatment of bipolar disorders.