Inflammatory and neurotrophic factor plasma levels are related to epilepsy independently of etiology

Objective Inflammation plays an essential role in epilepsy. Studies indicate that cytokines and neurotrophic factors can act in neuroexcitability and epileptogenesis. We aimed to investigate the association between plasma inflammatory and neurotrophic markers, seizure frequency, and chronic epilepsy...

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Published in:Epilepsia (Copenhagen) 2021-10, Vol.62 (10), p.2385-2394
Main Authors: Alvim, Marina K. M., Morita‐Sherman, Marcia E., Yasuda, Clarissa L., Rocha, Natália P., Vieira, Érica L., Pimentel‐Silva, Luciana R., Henrique Nogueira, Mateus, Barbosa, Renata, Watanabe, Nancy, Coan, Ana Carolina, Lopes‐Cendes, Iscia, Teixeira, Antonio L., Cendes, Fernando
Format: Article
Language:English
Subjects:
biomarkers
Brain-Derived Neurotrophic Factor
Ciliary Neurotrophic Factor
Convulsions & seizures
cytokines
Cytokines - metabolism
Epilepsy
Epilepsy - etiology
Epilepsy - metabolism
Epilepsy - pathology
Etiology
Glial Cell Line-Derived Neurotrophic Factor
Humans
Inflammation
Inflammation - metabolism
Interferon-gamma
Interleukin 1
Interleukin-10
Interleukin-17
Interleukin-2
Interleukin-4
Interleukin-6
Nerve Growth Factor
Neuronal-glial interactions
Neurotrophic factors
Neurotrophin 3
Neurotrophin 4
Plasma
Plasma levels
seizure frequency
Seizures
Tumor necrosis factor receptors
Tumor Necrosis Factor-alpha
Tumor necrosis factor-TNF
Tumor necrosis factor-α
γ-Interferon
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Summary:Objective Inflammation plays an essential role in epilepsy. Studies indicate that cytokines and neurotrophic factors can act in neuroexcitability and epileptogenesis. We aimed to investigate the association between plasma inflammatory and neurotrophic markers, seizure frequency, and chronic epilepsy subtypes. Methods We studied 446 patients with epilepsy and 166 healthy controls. We classified patients according to etiology and seizure frequency. We measured plasma levels of interleukin‐1 (IL‐1), IL‐2, IL‐4, IL‐6, IL‐10, IL‐17, interferon‐γ (IFNγ), tumor necrosis factor α (TNFα), soluble TNF receptor 1 (sTNFr1), sTNFr2, brain‐derived neurotrophic factor (BDNF), neurotrophic factor 3 (NT3), NT4/5, ciliary neurotrophic factor (CNTF), nerve growth factor (NGF), and glial cell line‐derived neurotrophic factor (GDNF) by enzyme‐linked immunosorbent assay or cytometric bead array. Results The plasma levels of BDNF, NT3, NGF, and sTNFr2 were higher, whereas IL‐2, IL‐4, IL‐6, IL‐10, IL‐17, IFNγ, TNFα, CNTF, and sTNFr1 were lower in patients than controls. IL1, GDNF, and NT4/5 were similar between groups. These markers did not correlate with age, sex, and epilepsy duration. The molecule sTNFr2 was the best marker to discriminate patients from controls (area under the curve = .857), also differing between patients with frequent and infrequent seizures. Significance This large cohort confirmed that patients with epilepsy have abnormal levels of plasma inflammatory and neurotrophic markers independent of the underlying etiology. Plasma level of sTNFr2 was related to seizure frequency and discriminated people with or without epilepsy with good accuracy, making it a potential biomarker for epilepsy and seizure burden.
ISSN:0013-9580
1528-1167
DOI:10.1111/epi.17023