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Multidimensional Approach Assessing the Role of Interleukin 1 Beta in Mesial Temporal Lobe Epilepsy
Renato O Santos1,2, Rodrigo Secolin1,2, Patrícia G Barbalho1,2
1Department of Translational Medicine, University of Campinas, Campinas, Brazil.
Abstract:
We aimed to investigate the role of interleukin-1 beta (IL-1β) in the mechanisms underlying mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE+HS). We assessed a cohort of 194 patients with MTLE+HS and 199 healthy controls. Patients were divided into those with positive and negative antecedent febrile seizures (FS). We used a multidimensional approach, including (i) genetic association with single nucleotide polymorphisms (SNPs) in the IL1B gene; (ii) quantification of the IL1B transcript in the hippocampal tissue of patients with refractory seizures; and (iii) quantification of the IL-1β protein in the plasma. We found a genetic association signal for two SNPs, rs2708928 and rs3730364*C in the IL1B gene, regardless of the presence of FS (adjusted p = 9.62e-11 and 5.14e-07, respectively). We found no difference between IL1B transcript levels when comparing sclerotic hippocampal tissue from patients with MTLE+HS, without FS, and hippocampi from autopsy controls (p > 0.05). Nevertheless, we found increased IL-1β in the plasma of patients with MTLE+HS with FS compared with controls (p = 0.0195). Our results support the hypothesis of a genetic association between MTLE+HS and the IL1B gene.
Insights
This study found a genetic link between the IL1B gene and mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE+HS). Interleukin-1 beta (IL-1β) protein levels were higher in MTLE+HS patients with a history of febrile seizures (FS).
Area of Science:
- Neuroscience
- Genetics
- Immunology
Background:
- Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE+HS) is a common form of drug-resistant epilepsy.
- The role of inflammation, particularly interleukin-1 beta (IL-1β), in MTLE+HS pathogenesis is not fully understood.
Purpose of the Study:
- To investigate the association between the IL1B gene and MTLE+HS.
- To examine the role of IL-1β in MTLE+HS, considering the influence of antecedent febrile seizures (FS).
Main Methods:
- Genetic association study using single nucleotide polymorphisms (SNPs) in the IL1B gene.
- Quantification of IL1B transcript in hippocampal tissue.
- Measurement of IL-1β protein levels in plasma.
Main Results:
- Significant genetic association found between two IL1B SNPs (rs2708928 and rs3730364*C) and MTLE+HS, irrespective of FS history.
- No significant difference in IL1B transcript levels in hippocampal tissue between MTLE+HS patients and controls.
- Elevated plasma IL-1β levels observed in MTLE+HS patients with a history of FS compared to controls.
Conclusions:
- The findings support a genetic association between the IL1B gene and MTLE+HS.
- IL-1β may play a role in MTLE+HS, particularly in patients with a history of febrile seizures, possibly through mechanisms not directly involving hippocampal IL1B transcript levels.
