Interictal alterations of cytokines and leukocytes in patients with active epilepsy

Nowak, Mareike; Bauer, Sebastian; Haag, Anja; Cepok, Sabine; Todorova-Rudolph, Anelia; Tackenberg, Björn; Norwood, Braxton A.; Oertel, Wolfgang H.; Rosenow, Felix; Hemmer, Bernhard; Hamer, Hajo M.

doi:10.1016/j.bbi.2010.10.022

Cited by 66 publications

(58 citation statements)

References 43 publications

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“…This finding is in line with previous studies reporting elevated cytokine levels in serum/plasma and CSF in the interictal period, but especially after seizures, in TLE and other epileptic syndromes [9,15,16,18,28,29]. The mechanisms underlying this low-grade inflammation, i.e.…”

Section: Inflammatory Association With Clinical Findingssupporting

confidence: 92%

“…The inclusion criteria for TLE were: diagnosis of TLE according to the ILAE criteria, age of more than 18 years, capacity to provide written informed consent, and seizure-free for at least 72 hoursreportedby the people with TLE and/ortheir companion. This period was chosenas previous studies showed that circulatingcytokines returned to basal levels at least 24 hours afterseizures [15,16]. All patients had temporal mesial sclerosis on magnetic resonance imaging (MRI).…”

Section: Methodsmentioning

confidence: 99%

“…For instance, one study reportedelevated frequencyof monocytes and NK cells in people with refractory epilepsy to antiepileptic drugs (AEDs) [15].…”

Section: Introductionmentioning

confidence: 99%

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Peripheral leukocyte profile in people with temporal lobe epilepsy reflects the associated proinflammatory state

Vieira

Oliveira

Lessa

et al. 2016

Brain, Behavior, and Immunity

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Section: Inflammatory Association With Clinical Findingssupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Peripheral leukocyte profile in people with temporal lobe epilepsy reflects the associated proinflammatory state

Vieira

Oliveira

Lessa

et al. 2016

Brain, Behavior, and Immunity

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“…IL-6 is a cytokine with both pro- and anti-inflammatory characteristics that mediates the acute phase reaction and fever. The predictive value of IL-6 is particularly interesting since IL-6 is the most consistently and chronically changed circulating cytokine in epilepsy [32,33,34]. However, other investigators failed to detect any cytokine changes that were of potential predictive value [18], possibly due to the fact that the changes were evaluated in epileptic adults using whole blood samples in vitro that were stimulated with lipopolysaccharide.…”

Section: Discussionmentioning

confidence: 99%

“…Firstly, VNS did not alter interictal cytokine levels. Since epilepsy patients are known to have altered interictal cytokine levels [32,33,34], we specifically determined whether VNS changed cytokine levels more than 12 h after a seizure. Nevertheless while these cytokine levels were unchanged, we cannot exclude the possibility that VNS treatment inhibits cytokine changes at a different time point.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Vagus Nerve Stimulation on Pro- and Anti-Inflammatory Cytokines in Children with Refractory Epilepsy: An Exploratory Study

Aalbers

Klinkenberg

Rijkers

et al. 2012

Neuroimmunomodulation

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Objectives: The vagus nerve has important immunological and anti-inflammatory actions that might be relevant to the beneficial effects of vagus nerve stimulation (VNS). Therefore, we conducted an exploratory study on VNS effects on cytokine levels in plasma and cerebrospinal fluid of children suffering from refractory epilepsy. Moreover, as predictors of the response are lacking, we also aimed to determine if cytokine changes predict the clinical response. Methods: VNS was performed according to a randomized double-blind design: plasma levels were compared between patients who received 20 weeks of high output (therapeutic) (n = 21) or low output (active control) stimulation (n = 20). Thereupon, all patients received high output stimulation for another 19 weeks; levels during this period were compared to baseline. Interictal interleukin-1β, interleukin-6, and interleukin-10 were determined by ELISA. Results: No significant changes were found between high and low output groups and between the last 19 weeks of stimulation and baseline. Changes in interleukin-1β correlated with improved IQ (τ = 0.42, p < 0.01). Lower baseline plasma levels of interleukin-6 were associated with more seizure frequency reduction [R² = 0.105 (1, 35), p = 0.050]. Conclusion: Interictal cytokine levels were not altered by VNS but baseline interleukin-6 predicted the clinical response. In the future, patient selection may be aided by determination of the cytokine profile of the patient.

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Brain temperature, brain metabolites, and immune system phenotypes in temporal lobe epilepsy

Mueller,

Hong,

Sharma

et al. 2024

Epilepsia Open

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ObjectiveEpileptogenesis is linked to neuroinflammation. We hypothesized that local heat production caused by neuroinflammation can be visualized non‐invasively in vivo via brain magnetic resonance spectroscopic imaging (MRSI) and MRSI‐thermometry (MRSI‐t) and that there is a relationship in patients with temporal lobe epilepsy (TLE) between MRSI‐t and brain metabolites choline and myo‐inositol and between neuroimaging and cellular and serum biomarkers of inflammation.MethodsThirty‐six (36) participants, 18 with temporal lobe epilepsy (13 females) and 18 age‐matched healthy controls (nine females), were enrolled prospectively and underwent MRSI/MRSI‐t; TLE participants also provided blood samples. Temperature was measured using creatine as a reference metabolite. Analysis of Functional NeuroImages 3dttest++ tool was used to analyze voxel‐level group differences in temperature, choline, and myo‐inositol. Associations with immune cell subsets, cytokines, and chemokines related to inflammation were quantified using correlation coefficients with significant relationships as noted.ResultsPatients with TLE showed elevated temperature, choline, and myo‐inositol in the temporal lobes. Higher brain temperature was associated with higher levels of cytokines and chemokines, including GM‐CSF, TNF, IL‐1β, and IL − 12p70, and lower frequency of immune cells including CD3+ T‐cells, CD4+ T‐cells, CD8+ T‐cells, and classical monocytes. Higher choline was associated with higher levels of the cytokines including LT‐α, IL‐13, and IL‐4, and higher myo‐inositol was associated with a higher frequency of CD4+ T‐cell and CD19+ B‐cell subsets and higher levels of cytokines and chemokines including LT‐α, IL‐13, and CCL3.SignificanceThis study, for the first time, showed that in temporal lobes of patients with TLE temperature and metabolite changes correlate with cellular and serum biomarkers of inflammation. Our results provide support for further development of MRSI‐t as a measure of neuroinflammation in epilepsy and potentially other neurological disorders and as an investigative and clinical tool.Plain Language SummaryNeuroinflammation is associated with excessive heat production which can be visualized with magnetic resonance spectroscopic imaging and thermometry (MRSI‐t). We prospectively investigated the relationship between MRSI‐t and cellular and serum measures of peripheral inflammation in patients with temporal lobe epilepsy (TLE); we compared the results of MRSI‐t in patients with TLE to healthy controls. We showed a relationship between the temperature elevations in TLE and elevations of various measures of peripheral inflammation. Our results support further development of MRSI‐t as a measure of neuroinflammation in epilepsy and potentially other neurological disorders and as an investigative and clinical tool.

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Interictal alterations of cytokines and leukocytes in patients with active epilepsy

Cited by 66 publications

References 43 publications

Peripheral leukocyte profile in people with temporal lobe epilepsy reflects the associated proinflammatory state

Peripheral leukocyte profile in people with temporal lobe epilepsy reflects the associated proinflammatory state

The Effects of Vagus Nerve Stimulation on Pro- and Anti-Inflammatory Cytokines in Children with Refractory Epilepsy: An Exploratory Study

Brain temperature, brain metabolites, and immune system phenotypes in temporal lobe epilepsy

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