Increased levels of HMGB1 and pro-inflammatory cytokines in children with febrile seizures

Abstract

ObjectiveFebrile seizures are the most common form of childhood seizures. Fever is induced by pro-inflammatory cytokines during infection, and pro-inflammatory cytokines may trigger the development of febrile seizures. In order to determine whether active inflammation, including high mobility group box-1 (HMGB1) and pro-inflammatory cytokines, occurs in children with febrile seizures or epilepsy, we analyzed cytokine profiles of patients with febrile seizures or epilepsy.MethodsForty-one febrile seizure patients who visited the emergency department of Seoul National University Boramae Hospital from June 2008 to May 2009 were included in this study. Blood was obtained from the febrile seizure child patients within 30 minutes of the time of the seizure; subsequently, serum cytokine assays were performed. Control samples were collected from children with febrile illness without convulsion (N = 41) and similarly analyzed. Serum samples from afebrile status epilepticus attacks in intractable epilepsy children (N = 12), afebrile seizure attacks in generalized epilepsy with febrile seizure plus (GEFSP) children (N = 6), and afebrile non-epileptic controls (N = 7) were also analyzed.ResultsSerum HMGB1 and IL-1β levels were significantly higher in febrile seizure patients than in fever only controls (p < 0.05). Serum IL-6 levels were significantly higher in typical febrile seizures than in fever only controls (p < 0.05). Serum IL-1β levels were significantly higher in status epilepticus attacks in intractable epilepsy patients than in fever only controls (p < 0.05). Serum levels of IL-1β were significantly correlated with levels of HMGB1, IL-6, and TNF-α (p < 0.05).ConclusionsHMGB1 and pro-inflammatory cytokines were significantly higher in febrile seizure children. Although it is not possible to infer causality from descriptive human studies, our data suggest that HMGB1 and the cytokine network may contribute to the generation of febrile seizures in children. There may be a potential role for anti-inflammatory therapy targeting cytokines and HMGB1 in preventing or limiting febrile seizures or subsequent epileptogenesis in the vulnerable, developing nervous system of children.

TRPV1 promotes repetitive febrile seizures by pro-inflammatory cytokines in immature brain

“…An increase in the release of pro-inflammatory cytokines, such as IL-1b, contributes to the generation of human febrile seizures and potentially induces long-lasting hyperexcitability and excitotoxicity that is associated with hippocampal epilepsy (Dube et al, 2005;Vezzani et al, 1999). Increases in HMGB1 might occur as a consequence of seizures (Choi et al, 2011;Maroso et al, 2010;Walker et al, 2014), which is consistent with our results that HMGB1 expression levels were elevated in the mouse hippocampus and cortex. Expression levels of IL-1b and HMGB1 in our experiments indicated that it was dependent upon TRPV1 activation (as no change was observed in IL-1b and HMGB1 release in the TRPV1 knockout mice).…”

Hydrogen Sulfide Promotes Learning and Memory and Suppresses Proinflammatory Cytokines in Repetitive Febrile Seizures

“…In many animal models of FSE, acute seizures cause glial activation and increased cytokine production [32,33] . In our study, microglia activation was particularly striking in the hippocampus; infiltrative microgliosis was associated with the upregulation of IL-1β and TNF-α.…”

Selected aspect of the epidemiology of febrile seizures in chil dren

“…Choi i wsp. w swojej pracy wykazali, że ryzyko wystąpienia drgawek gorączkowych częściej dotyczy chłopców niż dziewcząt i wynosi odpowiednio 71% vs. 29% [19]. W badaniach Gouurabi i wsp.…”

“…w swoich badaniach podają szczyt wystąpienia pierwszych drgawek gorączkowych u dzieci w wieku 2 lat [13], a także taką samą średnią wiekową uzyskali Fallah i wsp., badając grupę dzieci od 6. miesiąca życia do 6. roku życia [21]. Średnia wieku przypadająca na wystąpienie drgawek gorączkowych wśród dzieci koreańskich wyniosła 2,1 roku [19], a w populacji pacjentów irańskich 25 miesięcy [20]. W badaniach prowadzonych przez Jarrett i wsp.…”