Inhibitory effect of carbamazepine on inflammatory mediators produced by stimulated glial cells

Exposure of rat glial cells to lipopolysaccharide (LPS) induces the product ion of nitric oxide (NO) and prostaglandin E-2 (PGE(2)), the inflammatory m ediators implicated in the pathogenesis of seizures and epilepsy. To determ ine the effect of the anticonvulsant drug carbamazepine (CBZ) on the inflam matory process, LPS-stimulated rat primary glial cultures were exposed to t his agent. Dose-dependent inhibition of NO and PGE(2) production was observ ed of up to 77 and 88%, respectively. Furthermore, a prominent (94%,) decli ne in the secretory isoform of phospholipase A(2) (sPLA(2)) activity was fo und in response to CBZ and could contribute to the inhibition of PGE(2) pro duction. Cumulatively, our findings point to the anti-inflammatory effect o f CBZ on non-neuronal cells, which might, in part, contribute to its antico nvulsive effect. (C) 2000 Elsevier Science Ireland Ltd and the Japan Neuros cience Society. All rights reserved.