HMGB‐1, TLR4, IL‐1R1, TNF‐α, and IL‐1β: novel epilepsy markers?

Abstract

Aim: The purpose of this study was to compare HMGB‐1, TLR4, IL‐1β, IL‐1R1, and TNF‐α levels in patients with mild and severe epilepsy with those in a healthy control group. Methods: Children aged 4–17 years, diagnosed with epilepsy for at least three years and with no progressive neurological disease, metabolic disease or infection, were selected for the study. The severe epilepsy group consisted of 28 children with at least one episode a week despite receiving three or more antiepileptic drugs. The mild epilepsy group consisted of 29 children with no seizures in the previous year, receiving only one antiepileptic drug, while 27 healthy children were selected as the control group. HMGB‐1, TLR4, IL‐1R1, TNF‐α and IL‐1β levels were investigated in these three groups. The MRI findings and clinical characteristics of the patients in the epilepsy group were also compared with these markers. Results: HMGB‐1, TLR4, TNF‐α, and IL‐1β levels in the severe epilepsy group were higher than in the control group and the mild epilepsy group (p<0.05), and were higher in the mild epilepsy group than in the control group (p<0.05). IL‐1R1 was also higher in the severe epilepsy group than in the control group (p<0.05). Conclusion: In this first report to identity a possible correlation between HMGB‐1, TLR4, IL‐1β, IL‐1R1, and TNF‐α levels and severity of epilepsy, our data demonstrates that the serum level of these cytokines is higher in cases of drug‐refractory epilepsy.

Circulating P2X7 Receptor Signaling Components as Diagnostic Biomarkers for Temporal Lobe Epilepsy

“…Inflammatory mediators may also have diagnostic potential since levels of several inflammatory molecules have been found to be altered in the blood of patients with epilepsy [ 11 ]. This includes cytokines such as the pro-inflammatory cytokine IL-1β [ 12 , 13 , 14 , 15 ], HMGB1 [ 16 ], and the inflammation marker C-Reactive protein (CRP) [ 17 ].…”

“…Recent studies have shown P2X7R protein levels to be increased in the plasma of patients with underlying inflammation [ 30 ], including patients following sepsis [ 31 ]. Moreover, the expression of several cytokines downstream of P2X7R activation (e.g., IL-1β, IL-18) has been found altered in the blood of patients with epilepsy [ 12 , 13 , 14 , 15 , 32 ]. Whether P2X7R-dependent signaling can be used to support the diagnosis of epilepsy, has, however, not been investigated to date.…”

Advances in the Development of Biomarkers for Poststroke Epilepsy

“…Low-dose TNFα (5.0 μg/kg) significantly increased the frequency of epilepsy and prolonged the duration of neuronal firing [39,40]. The content of TNF-α was positively correlated with the severity of epilepsy, which was higher in the severe epilepsy group than in the mild group, while the nonepileptic group is at a minimum level [41]. Tumor necrosis factor is mainly involved in the pathological process of seizures through two receptors, which will induce seizures by binding receptor 1, while the activation of receptor 2 will exert anticonvulsant effects.…”

The performance of the alarmin HMGB1 in pediatric diseases: From lab to clinic

“…The complex interactions between immune‐inflammatory processes, cytokine activation, and genetic factors play important roles in the development of FS 99,100 . The levels of blood HMGB1 and IL‐1β in children with FS after 30 min of seizure attacks were significantly higher than those with fever only, and these two inflammatory indicators were correlated with each other 101–103 . HMGB1 contributes to the onset of FS and plays an important role in the occurrence of secondary epilepsy associated with the prolongation of FS, 104 and the occurrence of adult epilepsy is related to the recurrence of FS in childhood 105 .…”

“…HMGB1 contributes to the onset of FS and plays an important role in the occurrence of secondary epilepsy associated with the prolongation of FS, 104 and the occurrence of adult epilepsy is related to the recurrence of FS in childhood 105 . Similar to that of FS, serum HMGB1 was significantly elevated within 24 h of seizures in children with epilepsy and had the potential to predict seizure frequency and prognosis more accurately than IL‐1β 103,106 . Data from different experimental models of acute and chronic epilepsy have shown that HMGB1‐TLR4 signaling in the hippocampus plays a key role in the generation and recurrence of seizures 107 .…”