title: 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.
authors.affiliation: Department of Pharmacodynamics, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland. Electronic address: dariusz.andrzejczak@umed.lodz.pl.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Andrzejczak
authors.affiliation: Department of Pharmacodynamics, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Woldan-Tambor
authors.affiliation: Institute of Medical Biology PAS, Lodowa 106, 93-232 Lodz, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Bednarska
authors.affiliation: Department of Pharmacodynamics, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland.
authors.forename: Jolanta B
authors.initials: JB
authors.lastname: Zawilska
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000927:Anticonvulsants / Q000494:pharmacology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology; D008070:Lipopolysaccharides; D017628:Microglia / Q000187:drug effects* / Q000276:immunology*; D008928:Mitochondria / Q000187:drug effects / Q000276:immunology; D017208:Rats, Wistar; D000077236:Topiramate
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000927:Anticonvulsants; D016207:Cytokines; D008070:Lipopolysaccharides; D000077236:Topiramate; D005632:Fructose
keywords: Cytokines; Epilepsy; Microglial cells; Topiramate