interleukin-8 and Epilepsy--Temporal-Lobe

Our aim was to explore the association between plasma cytokines and febrile status epilepticus (FSE) in children, as well as their potential as biomarkers of acute hippocampal injury.. Analysis was performed on residual samples of children with FSE (n = 33) as part of the Consequences of Prolonged Febrile Seizures in Childhood study (FEBSTAT) and compared to children with fever (n = 17). Magnetic resonance imaging (MRI) was obtained as part of FEBSTAT within 72 h of FSE. Cytokine levels and ratios of antiinflammatory versus proinflammatory cytokines in children with and without hippocampal T2 hyperintensity were assessed as biomarkers of acute hippocampal injury after FSE.. Levels of interleukin (IL)-8 and epidermal growth factor (EGF) were significantly elevated after FSE in comparison to controls. IL-1β levels trended higher and IL-1RA trended lower following FSE, but did not reach statistical significance. Children with FSE were found to have significantly lower ratios of IL-1RA/IL-1β and IL-1RA/IL-8. Specific levels of any one individual cytokine were not associated with FSE. However, lower ratios of IL-1RA/IL-1β, IL-1RA/1L-6, and IL-1RA/ IL-8 were all associated with FSE. IL-6 and IL-8 levels were significantly higher and ratios of IL-1RA/IL-6 and IL-1RA/IL-8 were significantly lower in children with T2 hippocampal hyperintensity on MRI after FSE in comparison to those without hippocampal signal abnormalities. Neither individual cytokine levels nor ratios of IL-1RA/IL-1β or IL-1RA/IL-8 were predictive of MRI changes. However, a lower ratio of IL-1RA/IL-6 was strongly predictive (odds ratio [OR] 21.5, 95% confidence interval [CI] 1.17-393) of hippocampal T2 hyperintensity after FSE.. Our data support involvement of the IL-1 cytokine system, IL-6, and IL-8 in FSE in children. The identification of the IL-1RA/IL-6 ratio as a potential biomarker of acute hippocampal injury following FSE is the most significant finding. If replicated in another study, the IL-1RA/IL-6 ratio could represent a serologic biomarker that offers rapid identification of patients at risk for ultimately developing mesial temporal lobe epilepsy (MTLE).

Topics: Biomarkers; Brain Damage, Chronic; Child; Child, Preschool; Cytokines; Epilepsy, Temporal Lobe; Female; Hippocampus; Humans; Infant; Infant, Newborn; Interleukin 1 Receptor Antagonist Protein; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Risk Factors; Seizures, Febrile; Status Epilepticus

Data from animal models has nicely shown that inflammatory processes in the central nervous system (CNS) can modulate seizure frequency. However, a potential relationship between the modulation of seizure frequency and gene expression of key inflammatory factors in human epileptic tissue is still unresolved. Brain tissue from pharmacoresistant patients with mesial temporal lobe epilepsy (mTLE) provides a unique prerequisite for clinico-neuropathological correlations. Here, we have concentrated on gene expression of the human key inflammatory mediators, TLR4, ATF-3 and IL8, in correlation to seizure frequency and additional clinical parameters in human epileptic brain tissue of pharmacoresistant mTLE patients. Furthermore, we characterized the cell types expressing the respective proteins in epileptic hippocampi.. Total RNAs were isolated from n=26 hippocampi of pharmacoresistant mTLE patients using AllPrep DNA/RNA Mini Kit. cRNA was used for hybridization on Human HT-12 v3 Expression BeadChips with Illumina Direct Hybridization Assay Kit and resulting gene expression data was normalized based on the Illumina BeadStudio software suite by means of quantile normalization with background subtraction. Corresponding human hippocampal sections for immunohistochemistry were probed with antibodies against TLR4, ATF-3, IL8 and glial fibrillary acidic protein (GFAP), neuronal nuclear protein (NeuN) and the microglial marker HLA-DR.. We observed abundant TLR4 gene expression to relate to seizure frequency per month. For ATF-3, we found an inverse correlation of expression to seizure frequency. Lower expression of IL8 was significantly associated with high seizure frequency. Further, we detected TLR4 expression in neurons and GFAP-positive astrocytes of pharmacoresistant mTLE patients. Only neurons of human epileptic hippocampi express ATF-3. IL8 was expressed in microglia and reactive astrocytes.. Our results suggest a differential correlation of key inflammatory factor expression in epileptic hippocampi and seizure frequency in patients. The modulation of such processes may open new therapeutic perspectives for treating seizures.

Topics: Activating Transcription Factor 3; Astrocytes; Epilepsy, Temporal Lobe; Hippocampus; Humans; Inflammation; Interleukin-8; Neurons; Seizures; Toll-Like Receptor 4