Analysis of Plasma Multiplex Cytokines for Children With Febrile Seizures and Severe Acute Encephalitis

Abstract

We investigated the plasma cytokine profiles of children with febrile seizures or severe acute encephalitis using multiplex cytometry to evaluate the role of cytokines in these diseases. Interleukin-6, -10, -12p70, -17A, -2, -4, -5, -9, -13, -22, and -1β, interferon-γ, and tumor necrosis factor-α were measured in the plasma from children with febrile seizures (n = 9) or severe acute encephalitis (n = 21). In multivariate analysis, interleukin-6 was significantly increased in the plasma of the febrile seizure patients compared to those with severe acute encephalitis, suggesting that interleukin-6 is activated during the acute stage of a febrile seizure. A lower plasma interleukin-6 concentration was significantly associated with severe acute encephalitis. The cytokine network may be deregulated in severe acute encephalitis via the persistence of an uncontrolled inflammatory state in the brain.

Proinflammatory and anti-inflammatory cytokines in febrile seizures and epilepsy: systematic review and meta-analysis

“…Some related articles were excluded because of unvalued data (Dias De Sousa et al, 2012), lack of specific values (mean ± SD) ( Masuyama et al, 2002;Virta et al, 2002b;Ichiyama et al, 2004Ichiyama et al, , 2008Ichiyama et al, , 2009Stoeck et al, 2006;Yamanaka et al, 2006Yamanaka et al, , 2010Fukumoto et al, 2007;Sinha et al, 2008 Asano et al, 2010;Blyth et al, 2011;Mathieu et al, 2011;Haberlandt et al, 2013), lack of a control group without any neurological complications interfered with immunological response or using baseline references (Billiau et al, 2007;Alapirtti et al, 2009;Bauer et al, 2009;Li et al, 2013;Uludag et al, 2013), concomitant disorders in epileptic cases [e.g., depression (Lehtimäki et al, 2008) and neurocysticercosis (Evans et al, 1998)], concomitant disorders in the control group (e.g., encephalitis) (Ichiyama et al, 1998;Hu et al, 2014), and replicated data (Peltola et al, 2002). Some abstracts seemed to be related, but full-text was not available to make sure if they met the inclusion criteria or not (Ling et al, 1993;Kawakami et al, 1999b;Haspolat et al, 2002;Ganor et al, 2005;Makis et al, 2005;Lehtimäki et al, 2010;Lukaszewicz et al, 2010;Majoie et al, 2010;Mine et al, 2013).…”

Acute treatment with minocycline, but not valproic acid, improves long‐term behavioral outcomes in the Theiler's virus model of temporal lobe epilepsy

“…Reductions in seizure threshold in TMEV‐infected mice highlight its potential as a useful, and technically feasible biomarker of epileptogenesis; this would also provide a more cost‐effective surrogate for chronic video‐EEG recordings for moderate‐throughput drug studies. Changes in threshold that lead to symptomatic seizures are often associated with increased expression of inflammatory markers in animal seizure models and human patients . For example, transgenic mice that overexpress TNF‐α and IL‐6 demonstrate neurologic dysfunction including cell loss, decreased seizure threshold, and SRS .…”

“…The mechanisms by which viral encephalitis contributes to epilepsy are unclear, but the risk for developing epilepsy after viral encephalitis with seizures increases 22‐fold . It is likely that viral infection of the CNS underlies the development of chronic epilepsy due to increased expression of inflammatory cytokines, lowered seizure threshold, and increased risk of status epilepticus . In both the developed and developing world, infection‐induced encephalitis can promote the onset of temporal lobe epilepsy (TLE).…”

Evaluating an Etiologically Relevant Platform for Therapy Development for Temporal Lobe Epilepsy: Effects of Carbamazepine and Valproic Acid on Acute Seizures and Chronic Behavioral Comorbidities in the Theiler’s Murine Encephalomyelitis Virus Mouse Model

“…Human patients with viral infection-induced encephalitis who present with seizures during the acute infection period are up to 22 times more likely to develop spontaneous, unprovoked seizures than the general population (Annegers et al, 1988). More importantly, inflammation represents a significant risk factor for seizure induction and maintenance, with proinflammatory cytokines being highly expressed in various animal seizure models (Pernot et al, 2011;Vezzani and Friedman, 2011) and patients with epilepsy (Kan et al, 2012;He et al, 2013;Hu et al, 2014). In fact, some seizure-induced proinflammatory signaling molecules remain upregulated during epileptogenesis (VoutsinosPorche et al, 2004;Ravizza et al, 2008;Maroso et al, 2010) and may be essential to the establishment of spontaneous recurrent seizures associated with temporal lobe epilepsy (TLE) .…”