Chronically reduced IL-10 plasma levels are associated with hippocampal sclerosis in temporal lobe epilepsy patients

Abstract

Background: Increasing evidence supports the role of soluble inflammatory mediators in the pathogenesis of refractory temporal lobe epilepsy (TLE). Hippocampal sclerosis (HS) is a well-described pathohistological abnormality in TLE. The association of proinflammatory cytokines with epileptic disease profiles is well established; however, the potential significance of circulating interleukin 10 (IL-10), particularly in TLE-associated HS, is still poorly understood. Therefore, taking into consideration the neuroprotective and anticonvulsive effects of IL-10, we performed this study to examine the role of the plasma levels of IL-10 in patients with TLE with HS (TLE + HS), TLE without HS (TLE-HS) and with other types of epilepsy. Methods: This study included 270 patients with refractory epilepsy who were classified into four groups: i) 34 patients with TLE + HS, ii) 105 patients with TLE-HS, iii) 95 patients with extra-TLE (XLE) and iv) 36 patients with idiopathic generalized epilepsy (IGE). The plasma IL-10 levels were quantified using a commercially available enzyme-linked immunosorbent assay (ELISA). Results: IL-10 levels were significantly lower in TLE + HS than in TLE-HS (p = 0.013). In a subgroup of TLE-HS patients who had seizures 1 month before sampling, patients with seizures had significantly higher IL-10 levels than patients who were seizure-free (p = 0.039). Among a small group (n = 15) of non-refractory TLE-HS patients, IL-10 levels showed a moderate negative correlation with the duration of epilepsy (r = − 0.585, p = 0.023). Conclusions: This study demonstrated that chronically reduced levels of plasma IL-10 were associated with HS in TLE patients, suggesting that there was an inadequate systemic anti-inflammatory immune response. These results could provide new biological insights into the pathophysiology of HS in TLE. We also found that the production of IL-10 could be affected by the seizure frequency and declined concomitantly with increased disease durations. Therefore, the measurement of plasma IL-10 may have diagnostic value as a biomarker for stratifying TLE + HS from other epilepsy types or as a marker of disease progression towards a progressive form of epilepsy.

A 1-year follow-up study on immunological changes following deep brain stimulation in patients with epilepsy

“…Only one of nine responder patients had TLE, and the remaining had extra TLE or multifocal epilepsy, moreover, only two of 13 nonresponder patients had TLE. Considering the proinflammatory immune status as a principal component in TLE 10 , 14 , lower pre-DBS IL-10 levels in responders are unlikely to be a result of the epilepsy type, but the finding rather suggests the presence of an inadequate systemic anti-inflammatory immune response as one of the pathophysiological characteristics of chronic epilepsy 18 .…”

“…Taking into account the broad anti-inflammatory role of IL-10, an animal study revealed the role of IL-10 in the inhibition of IL-1beta production and inflammasome activation in microglia in response to epileptic seizures, suggesting a role for IL-10 in epilepsy treatment 17 . Recently, we detected reduced plasma IL-10 levels in patients with DRE, suggesting the presence of an inadequate systemic anti-inflammatory immune response during chronic epilepsy 18 .…”

MRI Features and Significance of Serum miRNAs and Inflammatory Cytokines in Patients with Temporal Lobe Epilepsy

“…Leo et al [21] demonstrated that anti-IL-6R antibodies were effective in reducing the number of absence seizures and depression-like behavior in a rat model of convulsive epilepsy, and they concluded that IL-6 plays an important role in seizure induction and seizure process. Basnyat et al [22] demonstrated that serum levels of IL-10 were significantly lower in patients with refractory TLE and that IL-10 levels showed a negative relationship with the course of epilepsy.…”

Advances in the Development of Biomarkers for Poststroke Epilepsy

“…With a strong anti-inflammation effect, IL-10 is known to suppress seizures in epilepsy patients by reducing the expression of interleukin-1 [34]. There is a significant negative correlation between plasma IL-10 levels and the prolongation of seizure time, while the continuous decrease of IL-10 has a significant positive correlation with hippocampal sclerosis in patients with epilepsy [35]. The significance of IL-10 in epilepsy remains controversial because some studies have reported that the level of IL-10 in patients with epilepsy is increased instead of decreased.…”