Increased plasma levels of cytokines after seizures in localization-related epilepsy

Lehtimäki, Kai; Keränen, Tapani; Palmio, Johanna; Mäkinen, Riikka; Hurme, Mikko; Honkaniemi, Jari; Peltola, Jukka

doi:10.1111/j.1600-0404.2007.00882.x

Cited by 112 publications

(98 citation statements)

References 12 publications

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“…This study shows the importance of epilepsy type in determining the chronic overproduction of IL-6 in refractory epilepsy, whereas our previous studies have demonstrated the acute activation of the cytokine network following seizures [8,9,20,21]. All patients with increased levels of IL-6 had TLE, which is known to be the most common epilepsy type refractory to drugs.…”

Section: Discussioncontrasting

confidence: 66%

“…However, the significance of clinical characteristics of epilepsy has not been well established in patients with possible immunological alterations. In our previous studies, titres of IL-6 measured at the beginning of video-EEG recordings before documented seizures and those measured between documented seizures during the recording have tended to be higher in patients with chronic epilepsy compared with healthy controls [20,21]. We have previously demonstrated an immediate effect of seizures on concentrations of IL-6 and to a lesser extent IL-1RA; the duration of this effect was less than 24 h. In this study, we aimed to assess long-term effects of seizure frequency on prevalence of IL-6 and IL-1RA.…”

Section: Introductionmentioning

confidence: 98%

“…We have previously demonstrated an immediate effect of seizures on concentrations of IL-6 and to a lesser extent IL-1RA; the duration of this effect was less than 24 h. In this study, we aimed to assess long-term effects of seizure frequency on prevalence of IL-6 and IL-1RA. IL-b levels were not measured here due to negative results in the previous studies [8,9,21]. In addition to seizure frequency, we evaluated the influence of epilepsy type, aetiology, and duration of epilepsy on the prevalence of elevated concentrations of IL-6 and IL-1RA in refractory focal epilepsy.…”

Section: Introductionmentioning

confidence: 99%

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Interleukin-6 levels are increased in temporal lobe epilepsy but not in extra-temporal lobe epilepsy

et al. 2009

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Previous studies have reported activation of inflammatory cytokines in seizures, but clinical characteristics of epilepsy associated with cytokine activation have not been well established. In this study, serum levels of interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1RA) were measured, and clinical characteristics of epilepsy were assessed in 86 well-evaluated patients with refractory focal epilepsy and in 5 patients with controlled focal epilepsy. Epilepsy was evaluated based on patient histories, electroclinical findings, and high-resolution brain MRI scans. Sixty-three healthy blood donors served as controls. IL-6 concentrations were chronically increased in epilepsy patients (11%) compared with healthy controls (0%) (P = 0.007). Increased levels of IL-6 were more prevalent in patients with temporal lobe epilepsy (TLE) compared to patients with extra-TLE (P = 0.028). Also the mean and the median serum levels of IL-6 were higher in patients with TLE than in patients with extra-TLE (P = 0.042). Concentrations of IL-1RA were not significantly different in patients compared with controls. Indicated by increased levels of IL-6 in TLE, epilepsy type is important in determining chronic overproduction of cytokines in refractory focal epilepsy. The results may reflect a chronic immunological process in the brain in patients with refractory epilepsy.

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Section: Discussioncontrasting

confidence: 66%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Interleukin-6 levels are increased in temporal lobe epilepsy but not in extra-temporal lobe epilepsy

et al. 2009

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“…On the other hand, if VNS only inhibits cytokine expression in the immediate postictal phase, this effect would not be detected using the present study design. Although it is technically challenging, future studies should compare cytokine levels immediately before and after a seizure [35,36]. …”

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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“…Our previous studies have revealed that the levels of cytokines IL-6, IL-1 ␤ and IL-1ra are increased in serum or plasma after seizures [11][12][13][14] . In cerebrospinal fluid (CSF), only increased levels of IL-6 were evident after single tonic-clonic seizure, whereas IL-1 ␤ and IL-1ra levels remained unchanged [2,11] .…”

Section: Introductionmentioning

confidence: 99%

Levels of IL-1β and IL-1ra in Cerebrospinal Fluid of Human Patients after Single and Prolonged Seizures

Lehtimäki

Keränen²,

Palmio³

et al. 2009

Neuroimmunomodulation

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Background: Experimentally induced seizures are associated with increased production of inflammatory cytokines in the nervous system. Elevated cerebrospinal fluid levels of cytokine interleukin-6 (IL-6) have been found after a single generalized seizure in human patients. After prolonged seizures, levels of IL-6 have been shown to be even higher compared with single seizures. In the present study, we determined the levels of proconvulsive IL-1β and anticonvulsive IL-1ra in cerebrospinal fluid after single tonic-clonic seizures as well as after prolonged seizures. Methods: The levels of cytokines were measured using enzyme-linked immunosorbent assay. Results: We found that after single seizures, a slight increase in anticonvulsive IL-1ra levels was found; however, after prolonged partial or recurrent tonic-clonic seizures, the levels of IL-1ra were significantly elevated, together with decreased IL-1β levels. Conclusion: Our results indicate that after severe seizures, the balance between IL-1-type cytokines is changed towards a neuroprotective and anticonvulsive direction with an overproduction of IL-1ra with respect to potentially neurotoxic IL-1β. This reaction may serve as a defense mechanism of the nervous system against excitotoxic neuronal damage.

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Increased plasma levels of cytokines after seizures in localization-related epilepsy

Abstract: These results show that only single seizures cause activation of cytokine cascade and associated inflammatory signals. In the case of recurrent seizures, these signals may result in structural changes in the nervous tissue, which are generally associated with drug refractory epilepsy.

Cited by 112 publications

References 12 publications

Interleukin-6 levels are increased in temporal lobe epilepsy but not in extra-temporal lobe epilepsy

Interleukin-6 levels are increased in temporal lobe epilepsy but not in extra-temporal lobe epilepsy

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

Levels of IL-1β and IL-1ra in Cerebrospinal Fluid of Human Patients after Single and Prolonged Seizures

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