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

Exposure of rat glial cells to lipopolysaccharide (LPS) induces the production of nitric oxide (NO) and prostaglandin E-2 (PGE(2)), the inflammatory mediators implicated in the pathogenesis of seizures and epilepsy. To determine the effect of the anticonvulsant drug carbamazepine (CBZ) on the inflammatory process, LPS-stimulated rat primary glial cultures were exposed to this agent. Dose-dependent inhibition of NO and PGE(2) production was observed of up to 77 and 88%, respectively. Furthermore, a prominent (94%,) decline in the secretory isoform of phospholipase A(2) (sPLA(2)) activity was found in response to CBZ and could contribute to the inhibition of PGE(2) production. Cumulatively, our findings point to the anti-inflammatory effect of CBZ on non-neuronal cells, which might, in part, contribute to its anticonvulsive effect. (C) 2000 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved.