Pretreatment with TLR ligands resulted in decreased seizure severity, lower hippocampal pro-inflammatory (IL-1β and IL-6) cytokines and higher anti-inflammatory (IL-10 and TGF- β) mediators in the pilocarpine-treated rats.
Statistically noticeable (p = 0.0630) was that approximately 10% of dog with epilepsy (R<sup>2</sup> = 0.105) had increased seizure frequency and IL-1β elevation.
To investigate the chronic effects of raised Interleukin-1β on seizures, the sodium currents of hippocampal neurons were recorded by whole-cell voltage clamp.
The treatment with dexamethasone decreased the severity of seizures, also decreased TNF-alpha and Interleukin 1 beta levels in the hippocampus and TNF-alpha level in the serum.
Receiver operating characteristic curve analysis revealed that HMGB1 could more accurately predict seizure frequency than IL-1β; when the serum concentration of HMGB1 was >9.625 ng/mL, there was 80.6% sensitivity and 92.5% specificity for predicting seizure frequency reduction.
DEX reduced seizure severity and increased the amplitudes and sustainable time of LTP, and also inhibited the hippocampal expression of α7-nAChR and IL-1β in CSE rats.
This study was carried out to compare GRIN2B, BDNF, and IL-1β gene expressions in 50 patients suffering from generalized epilepsy with tonic-colonic seizures and 50 age- and sex-matched healthy subjects using TaqMan Real-time PCR.
Here we show that blocking IL-1β receptors with anakinra, the human recombinant form of the endogenous IL-1 receptor antagonist used to treat rheumatoid arthritis, normalizes hippocampal neurotransmission and reduces seizure susceptibility in a CJD mouse model.
We recently discovered that forebrain activation of the IL-1 receptor/Toll-like receptor (IL-1R1/TLR4) innate immunity signal plays a pivotal role in neuronal hyperexcitability underlying seizures in rodents.
In this study we investigated whether three different COX-2 inhibitors alter pentylenetetrazol (PTZ)-induced seizures and increase of interleukin-1β (IL-1β), interleukin-6 (IL-6), interferon-γ (INF-γ), tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) levels in the hippocampus and cerebral cortex of mice.
Our results revealed that 10μg ST2825 markedly reversed the increased Tyr<sup>1472</sup>-phosphorylation of the NR2B subunit of NMDA receptor observed in the proconvulsant conditions of IL-1β and in seizures induced by pilocarpine alone.
Thus, this work identifies a pathogenic role of postnatal IL-1β/IL-1R1 pathway and subsequent prolonged prominent increase of endocannabinoid signaling in adult seizure susceptibility following prolonged FS, and highlights IL-1R1 as a potential therapeutic target for preventing the development of epilepsy after infantile FS.
Among different proinflammatory cytokines, interleukin-1β (IL-1β) has been shown to be significantly involved in epileptogenesis and maintenance of seizures.
Our study demonstrated that GluN2B phosphorylation at Tyr1472 site mediated by the transient increase of IL-1β was involved in the enhanced adult seizure susceptibility after prolonged FSs, implicating GluN2B-containing NMDAR is a new potential drug target with a wide therapeutic time window to prevent epileptogenesis in patients with infantile FSs.
These data are the first to demonstrate that the inflammatory response induced by IL-1β promotes seizures and plays an important role in the pathogenesis of MTLE via the PI3K/Akt/mTOR signaling pathway.
To understand the role of genes encoding pro-inflammatory cytokines in epilepsy, this study aimed to evaluate the polymorphisms of the promoter regions of IL-1β-511C>T (rs16944), TNF-α-308G>A (rs1800629) and IL-6-174G>C (rs1800795) genes and to look into the interaction between these genes in influencing seizure susceptibility, seizure frequency and response to therapy.
In particular, the IL-1 receptor (R)/Toll-like receptor (TLR) signaling pathways are activated in experimental models of seizures and in human epileptic tissue from drug-resistant patients.
Three lines of evidence suggest a role for IL-1: brain tissue from epilepsy patients and brain tissue from animal models shows increased IL-1 expression after seizures, and IL-1 has proconvulsive properties when applied exogeneously.
The results suggest that the increased IL-1beta expressions in the prefrontal cortex and hippocampus induced by norfloxacin with biphenylacetic acid relate to seizure activities, and that these brain regions play pivotal roles in norfloxacin-induced convulsions.
We immunocytochemically investigated the brain expression and cellular distribution pattern of IL-1beta, IL-1 receptor (IL-1R) types I and II and IL-1R antagonist (IL-1Ra) in FCD and GNT specimens, and we correlate these parameters with the clinical history of epilepsy in patients with medically intractable seizures.