Interictal interleukin‐17A levels are elevated and correlate with seizure severity of epilepsy patients

Abstract

SUMMARYInterleukin 17A (IL-17A) is implicated in the pathogenesis of several neuroimmunologic diseases. We aimed to evaluate the relationship between IL-17A and seizure severity in patients with epilepsy. Seventy patients with probable symptomatic epilepsy and 68 healthy controls were included. Interictal serum IL-17A and related cytokine (IL-23, IL-6, IL-1b, interferon gamma (IFN-c), and IL-10) levels were measured. The relationship between seizure severity and cytokine concentrations was assessed by Spearman correlation and multivariate linear regression test. IL-17A levels in the cerebrospinal fluid (CSF) were tested in 30 additional patients with epilepsy, either in the postictal or interictal period and 15 patients with idiopathic inflammatory demyelinating diseases (IIDDs). Interictal serum IL-17A levels were significantly elevated in patients with epilepsy compared to controls. IL-6, IFN-c, and IL-1b levels were also markedly elevated. Spearman correlation analysis revealed positive correlation between IL-17A, IL-6 levels and Veterans Administration Seizures Frequency and Severity Rating Scale score (VA score); IFN-c, IL-10 levels, and National Hospital Seizure Severity Scale (NHS3) score. In addition, IL-17A levels correlated significantly with seizure frequency. Multivariate linear regression test showed that only IL-17A levels were independently positively correlated with VA scores (B = 0.288, p = 0.027). Postictal IL-17A levels in the CSF were significantly elevated compared to interictal patients and patients with IIDDs. Our results suggest that interictal IL-17A levels correlated highly with seizure severity.

IL-1β, IL-6 and IL1Ra levels in temporal lobe epilepsy

“…Lehtimä ki et al found higher serum IL-6 levels in epileptic patients with intellectual disability than the controls [18]. Inter-ictal serum IL1b levels were elevated in patients with epilepsy compared to controls [4]. A recent study found interictal elevation of IL-6 but not of IL-1b [1].…”

“…Among different inflammatory cytokines studied such as TNF-a and IL-17A, it has been IL-6, IL-1b and IL-1Ra which have attracted most attention in clinical studies [1][2][3][4].…”

Magnesium Sulfate Prevents Placental Ischemia-Induced Increases in Brain Water Content and Cerebrospinal Fluid Cytokines in Pregnant Rats

“…A direct role for IL-17 in mediating hypertension during pregnancy was demonstrated using animal studies where infusion of IL-17 into the pregnant rat increased mean arterial pressure and oxidative stress (Dhillion et al, 2012) while reducing IL-17 in placental ischemic rats attenuates blood pressure and oxidative stress (Cornelius et al, 2013). While there are no reports of changes in IL-17 levels following eclamptic seizures, there are reports that IL-17 is increased in the circulation of epilepsy patients in between seizures or following seizures and IL-17 levels was correlated with seizure frequency and severity in epilepsy patients (Mao et al, 2013). CSF IL-17 levels were also elevated in patients between seizure episodes (Mao et al, 2013) and were correlated with glutamate levels and BBB disruption in a group of multiple sclerosis patients (Kostic et al, 2014).…”

“…While there are no reports of changes in IL-17 levels following eclamptic seizures, there are reports that IL-17 is increased in the circulation of epilepsy patients in between seizures or following seizures and IL-17 levels was correlated with seizure frequency and severity in epilepsy patients (Mao et al, 2013). CSF IL-17 levels were also elevated in patients between seizure episodes (Mao et al, 2013) and were correlated with glutamate levels and BBB disruption in a group of multiple sclerosis patients (Kostic et al, 2014). Furthermore, IL-17 has been shown to induce BBB disruption through the production of reactive oxygen species and down-regulation of Occludin (a tight junction protein) (Huppert et al, 2010).…”

Intestinal Microbiota as an Alternative Therapeutic Target for Epilepsy

“…The levels of proinflammatory cytokines such as interleukin 6 (IL-6) and interferon γ in the peripheral blood of the epileptic patients are usually higher than those of control patients, implicating the role of immune factors in the disease process of epilepsy [45]. Recently, it was reported that the level of IL-17A, either in the cerebrospinal fluid (CSF) or in the peripheral blood of patients with epilepsy, was significantly elevated and the level of IL-17A was highly correlated with seizure frequency and severity [46]. IL-17A is the canonical cytokine produced by the helper T (Th) cell 17 subset of lymphocytes.…”