interleukin-8 and Seizures

Omicron generally causes milder disease than previous strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially in fully vaccinated individuals. However, incompletely vaccinated children may develop Omicron-related complications such as those affecting the central nervous system. To characterize the spectrum of clinical manifestations of neuro-COVID and to identify potential biomarkers associated with clinical outcomes, we recruited 15 children hospitalized for Omicron-related neurological manifestations in three hospitals in Hong Kong (9 boys and 6 girls aged 1-13 years). All were unvaccinated or incompletely vaccinated. Fourteen (93.3%) were admitted for convulsion, including benign febrile seizure (n = 7), complex febrile seizure (n = 2), seizure with fever (n = 3), and recurrent breakthrough seizure (n = 2), and the remaining nonconvulsive patient developed encephalopathic state with impaired consciousness. None of the seven children with benign febrile seizure and six of eight children with other neurological manifestations had residual deficits at 9-month follow-up. SARS-CoV-2 RNA was undetectable in the cerebrospinal fluid (CSF) specimens of seven patients who underwent lumbar puncture. Spike-and-wave/sharp waves affecting the frontal lobes were detected in four of seven (57.1%) patients who underwent electroencephalogram. Children with Omicron-related neurological manifestations had significantly higher blood levels of IL-6 (p < 0.001) and CHI3L1 (p = 0.022) than healthy controls, and higher CSF levels of IL-6 (p = 0.002) than children with non-COVID-19-related febrile illnesses. Higher CSF-to-blood ratios of IL-8 and CHI3L1 were associated with longer length of stay, whereas higher ratios of IL-6 and IL-8 were associated with higher blood tau level. The role of CSF:blood ratio of IL-6, IL-8, and CHI3L1 as prognostic markers for neuro-COVID should be further evaluated.

Topics: Child; COVID-19; Female; Humans; Interleukin-6; Interleukin-8; Male; RNA, Viral; SARS-CoV-2; Seizures; Seizures, Febrile

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

We investigated changes in the levels of significant cytokines in relation to neonatal seizures, a pattern of cytokine concentrations serially and the severity of brain insult. The hypoxic-ischaemic encephalopathy-induced seizure group consisted of 13 patients, and another 15 normal newborns were enrolled as a control group. All of the initial samples were obtained within the first 24 h of admission, and the second samples were obtained between 48 and 72 h in both groups. Only the third samples were taken in the seizure group on the 5th day. During neonatal seizures, the levels of most cytokines increased within 24 h, and, in particular, the levels of interleukin (IL)-8 significantly increased (P < 0.05). After 48-72 h of seizure onset, the levels of most cytokines decreased, especially, IL-1Ra; however, IL-8 and IL-10 remained increased (P < 0.05). During the prognosis, one patient who was diagnosed with quadriplegic cerebral palsy at 6 months of age presented extreme elevation of IL-1beta, IL-1Ra, IL-6, IL-8, IL-10 and tumor necrosis factor-alpha in the initial sample, reflecting the severity of brain damage. A significant increase in IL-8 may serve as a biomarker for earlier detection of brain damage in neonatal seizure, if detected within 24 and 48-72 h of the seizure.

Topics: Biomarkers; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hypoxia-Ischemia, Brain; Infant, Newborn; Interleukin 1 Receptor Antagonist Protein; Interleukin-10; Interleukin-8; Male; Seizures

Symptoms originating from the central nervous system (CNS) occur frequently in patients with systemic lupus erythematosus (SLE), and CNS involvement in lupus is associated with increased morbidity and mortality. We recently showed that neurones and astrocytes are continuously damaged during the course of CNS lupus. The matrix metalloproteinases (MMPs) are a group of tissue degrading enzymes that may be involved in this ongoing brain destruction. The aim of this study was to examine endogenous levels of free, enzymatically active MMP-2 and MMP-9 in cerebrospinal fluid from patients with SLE. A total of 123 patients with SLE were evaluated clinically, with magnetic resonance imaging of brain and cerebrospinal fluid (CSF) analyses. Levels of free MMP-2 and MMP-9 were determined in CSF using an enzymatic activity assay. CSF samples from another 22 cerebrally healthy individuals were used as a control. Intrathecal MMP-9 levels were significantly increased in patients with neuropsychiatric SLE as compared with SLE patients without CNS involvement (P < 0.05) and healthy control individuals (P = 0.0012). Interestingly, significant correlations between MMP-9 and intrathecal levels of neuronal and glial degradation products were noted, indicating ongoing intrathecal degeneration in the brains of lupus patients expressing MMP-9. In addition, intrathecal levels of IL-6 and IL-8--two cytokines that are known to upregulate MMP-9--both exhibited significant correlation with MMP-9 levels in CSF (P < 0.0001), suggesting a potential MMP-9 activation pathway. Our findings suggest that proinflammatory cytokine induced MMP-9 production leads to brain damage in patients with CNS lupus.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Brain; Central Nervous System Diseases; Cerebrospinal Fluid Proteins; Enzyme Induction; Female; Glial Fibrillary Acidic Protein; Humans; Interleukin-6; Interleukin-8; Leukocytosis; Lupus Erythematosus, Systemic; Magnetic Resonance Imaging; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Meningitis, Aseptic; Middle Aged; Myelitis, Transverse; Nerve Tissue Proteins; Psychotic Disorders; Seizures; tau Proteins