Local production of TNF alpha and IL-1 beta in the brain may be involved in the enhanced seizure response of mice after administration of S. dysenteriae.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.