Immunomodulatory Effects of Anti-Epileptic Drug Lacosamide on Mammalian Macrophages.

Unforeseen immunotoxic activity and/or a lack of efficacy against the inflammatory components of diseases remain two common reasons for which many drug candidates fail clinical trials. There is growing evidence that neuroinflammation plays a critical role in the pathophysiology of epilepsy, thus suggesting that AEDs possessing anti-inflammatory properties may ensure superior therapeutic outcomes. Antiepileptic medications (AEDs) with anti-inflammatory qualities may provide better therapeutic value since neuroinflammation is becoming more widely acknowledged as an important component in the pathophysiology of epilepsy. This study aimed to examine the possible immunomodulatory effects on an in vitro mammalian macrophage cell line (J774.2) of Lacosamide (LCM), a third-generation AED with a unique mode of action. The effects of lacosamide cytotoxicity (1, 5, and 10 μg/mL) on the production of pro-inflammatory cytokines TNF-α, IL-6, GM-CSF, and IL-12p40 in LPS-induced macrophages were assessed using ELISA. Lacosamide’s non-toxic profile was confirmed by the results, which showed that it did not affect cell viability at the tested concentrations. However, in LPS-stimulated macrophages, lacosamide exhibits a fairly potent anti-inflammatory effect. Here, we demonstrate that lacosamide significantly and dose-dependently reduces TNF-α and IL-6 levels (*,**) and, at high doses, strongly inhibits the release of IL-12p40 (***). However, there was no discernible impact on GM-CSF levels. Such a selective modulation may suggest that the action of Lacosamide is focused on specific inflammatory signaling pathways rather than on the general suppression of immune response. These findings indicate that, in addition to its anticonvulsant properties, lacosamide possesses intrinsic anti-inflammatory potential that can modulate immune responses. The identification of lacosamide immunomodulatory properties sets the ground for understanding its overall clinical profile, especially in cases of drug-resistant epilepsy with an inflammatory component. Thus, further investigations involving general immune cells and the associated signaling pathways will define the emerging role of lacosamide as a potential therapeutic strategy targeting neuroinflammation in neurological conditions.