Evaluation of immunomodulatory effects of lamotrigine in BALB/c mice

Abstract

Modulation of the immune system has recently been shown to be involved in the pharmacological effects of old antiepileptic drugs and in the pathogenesis of epilepsy. Therefore, the most recent guidelines for immunotoxicological evaluation of drugs were consulted to investigate the immunomodulatory effects of lamotrigine, a newer antiepileptic drug, in BALB/c mice. These included the in vivo effects of lamotrigine on delayed-type hypersensitivity (DTH) response to sheep red blood cell (SRBC) antigens, hemagglutination titer assays and hematological changes. In vitro effects of lamotrigine on ConA-induced splenocyte proliferation and cytokine secretion were assessed. The results showed that lamotrigine treatment significantly increased the DTH response to SRBC in the mouse model of this study. This was accompanied by a significant increase in relative monocyte and neutrophil counts and in spleen cellularity. Lamotrigine significantly inhibited ConA-induced splenocyte proliferation in vitro and it significantly inhibited IL-2 and TNF-α secretion in ConA-stimulated splenocytes. In conclusion, the results demonstrated significant immunomodulatory effects of lamotrigine in BALB/c mice. These data could expand the understanding of lamotrigine-induced adverse reactions and its role in modulating the immune system in epilepsy.

Pregabalin inhibits in vivo and in vitro cytokine secretion and attenuates spleen inflammation in Lipopolysaccharide/Concanavalin A -induced murine models of inflammation

“…Besides, the investigation on peritoneal macrophages is supported by the emerging role of monocytes in promoting brain inflammation and exacerbation of neuronal damage in (2020) 10:4007 | https://doi.org/10.1038/s41598-020-61006-1 www.nature.com/scientificreports www.nature.com/scientificreports/ neuroinflammatory conditions such as status epilepticus 37 . The doses of the mitogens, and the time points for cytokine measurements were selected based on previous studies and on optimization experiments [21][22][23][24][25]28,30 . In LPS-model of neuroinflammatory conditions, seizure and anxiety, LPS was used at doses of 0.01-3 mg/kg [21][22][23][24]28 .…”

“…The doses of the mitogens, and the time points for cytokine measurements were selected based on previous studies and on optimization experiments [21][22][23][24][25]28,30 . In LPS-model of neuroinflammatory conditions, seizure and anxiety, LPS was used at doses of 0.01-3 mg/kg [21][22][23][24]28 . In this study, a dose of 0.1 mg/kg was used to induce inflammation in mice while keeping minimal lethality, and to allow the moderate anti-inflammatory effect of PGB to be significantly observed.…”

“…In this study, a dose of 0.1 mg/kg was used to induce inflammation in mice while keeping minimal lethality, and to allow the moderate anti-inflammatory effect of PGB to be significantly observed. In the ConA-model of inflammation, the dose and the concentration used were based on our previous studies 28,30 . The 2-hour time point for cytokines measurement after LPS administration in vivo was previously shown to significantly increase IL-6, TNF-α, IL-1β and IL-2 levels in LPS-induced inflammation in mice 25,30 .…”

“…The 2-hour time point for cytokines measurement after LPS administration in vivo was previously shown to significantly increase IL-6, TNF-α, IL-1β and IL-2 levels in LPS-induced inflammation in mice 25,30 . In vitro, cytokines were previously measured after 24, 48 and 72 hours of mitogen administration in BALB/c mice 28,30 .…”

“…Spleens were minced between the frosted edges of two microscopic slides and the cells were then pooled and centrifuged at 1200 rpm for 7 min at 4 °C. The red blood cells (RBC) within the pellets were then lysed at RT for 3 min using RBC lysis buffer as previously described 27,28 . Splenocytes were then suspended in 1 mL of RPMI-10% FBS and viable splenocyte count was determined using trypan blue dye exclusion method 29 .…”