The effects of topiramate on lipopolysaccharide (LPS)-induced proinflammatory cytokine release from primary rat microglial cell cultures

Abstract

A growing body of evidence suggests that inflammatory processes and activation of glial cells could contribute to seizures and epileptogenesis. In various animal studies on epilepsy, proinflammatory cytokines have been demonstrated to exert a proconvulsive activity. On the other hand, it is suggested that antiepileptic drugs could modulate immune system activity. The aim of the present study was to investigate whether topiramate, a new generation antiepileptic drug with a complex mechanism of action, could affect the lipopolysaccharide (LPS)-induced release of TNF-α, IL-1β and IL-6 from primary rat microglial cell cultures. Proinflammatory cytokines were measured in supernatants of primary rat microglial cell culture with enzyme-linked immunosorbent assay kits. Additionally, the effect of the drug on LPS-evoked changes in mitochondrial metabolic activity was evaluated with the aid of the MTT test. Topiramate (1, 10, 100μg/ml; 24h incubation) produced a statistically significant decrease in LPS-stimulated IL-1β and IL-6 levels from primary rat microglial cells in a concentration-dependent manner. The drug used at a concentration of 100μg/ml also significantly suppressed TNF-α release. Incubation of microglial cells with topiramate for 24h prevented the LPS-induced increase in their mitochondrial activity. It is suggested that the anti-cytokine action of topiramate could provide an additional mechanism in its antiepileptic activity.

Keywords: Cytokines; Epilepsy; Microglial cells; Topiramate.