Cytokine levels in febrile seizure patients: A systematic review and meta-analysis.

PURPOSE: Febrile seizures (FSs) are the most common form of childhood seizures. During infection, both pro-inflammatory and anti-inflammatory cytokines are produced. Complex interactions among immune-inflammatory process, cytokine activation, and genetic factors are involved in the pathogenesis of FSs. The association between cytokines and FSs during childhood is inconclusive due to inconsistent results reported in different studies. We performed a systematic review and meta-analysis to determine an association between cytokines and FS in children. METHODS: We searched PubMed, EMBASE, and Cochrane databases for studies published up to January 2017 using the following key words: ["cytokine" OR "interleukin" OR "tumor necrosis factor alpha" OR "interferon-gamma" OR "single nucleotide polymorphism"] AND ["febrile seizure" OR "febrile convulsion"] AND ["pediatric" OR "infant" OR "child"]. Standardized mead difference (SMD) and 95% confidence intervals (CI) were calculated using standard meta-analysis techniques. RESULTS: A total of 6 studies enrolling 243 children with FS and 234 controls were included in the meta-analysis. A total of 4 different inflammatory mediators were. The results indicated that CSF IL-1ß level and serum IL-6 level were significantly associated with FS (CSF IL-1ß: SMD, 1.064; 95% CI, 0.217-1.611; P < 0.01, serum IL-6 SMD, 2.654; 95% CI, 2.332-2.975; P < 0.01). CONCLUSION: The results of this meta-analysis suggest that CSF IL-1ß level and serum IL-6 level are associated with an increased risk of FSs in children. Based on these results, it is expected that a therapeutic agent for specific cytokines could be developed in the future to prevent FS.

Interleukin-4 and tumor necrosis factor-alpha levels in children with febrile seizures.

PURPOSE: The pathophysiology of febrile seizures remains unclear. Cytokines have been suggested to play a role in the pathogenesis of febrile seizures. We compared TNF-α and IL-4 levels in patients with febrile seizure (FS) with those in controls and identified the relationship between cytokines and various other factors. METHOD: Fifty FS patients who visited Konkuk University Hospital from December 2015 to December 2016 were included. Thirty-nine patients who had fever without seizures were enrolled as the control group. Serum samples from febrile patients with a history of febrile seizures without present seizures (FPH) (N = 12) and from the afebrile seizure (AF) group (N = 13) were also analyzed. In the FS group, we compared cytokine levels among patients stratified by sex, family history, seizure recurrence, duration of seizure and serum lactate levels. RESULTS: The median serum TNF-α level in the FS group (19.54 pg/mL) was significantly higher than that in the control group (15.86 pg/mL). Higher median serum IL-4 levels were detected in the FS group (3.38 pg/mL) than in the control group (3.30 pg/mL). In the FS group, the serum IL-4 and TNF-α levels correlated with seizure recurrence and serum lactate levels, but they did not correlate with family history, duration of seizures or sex. CONCLUSIONS: Our study supports the hypothesis that TNF-α production is involved in the pathogenesis of febrile seizures. IL-4 is believed to be involved in the pathogenesis of febrile seizures. The number of seizures and lactate levels were correlated with IL-4 and TNF-α levels.

Correction to: Analysis of plasma multiplex cytokines and increased level of IL-10 and IL-1Ra cytokines in febrile seizures.

After publication of the article [1], it has been brought to our attention that several of the authors' names were formatted incorrectly in the original version of the article. The corrections are listed below -"Byungok Kwak" should be "Byung Ok Kwak""Soojin Kim" should be "Soo-Jin Kim""Sunwhan Bae" should be "Sun Whan Bae""Jaesung Son" should be "Jae Sung Son""Soonyung Kim" should be "Soo-Nyung Kim"The original version of the article has now been revised.

Analysis of plasma multiplex cytokines and increased level of IL-10 and IL-1Ra cytokines in febrile seizures.

BACKGROUND: Febrile seizures are the most common form of childhood seizures. Fever generation involves many cytokines, including both pro- and anti-inflammatory cytokines. Some of these cytokines also induce febrile seizures. We compared cytokine production in children with a fever alone (healthy control group) and febrile seizure children group. Also, we evaluated the cytokine level of children with a fever alone and febrile seizure history. METHODS: Fifty febrile seizure patients and 39 normal control patients who visited the emergency department of Konkuk University Hospital from December 2015 to December 2016 were included in this study. Blood was taken from the peripheral vessels of children in all groups within 1 h of the seizure, and serum was obtained immediately. Serum samples from patients with only a fever and a febrile seizure history (N = 13) and afebrile seizure controls (N = 12) were also analyzed. RESULTS: The serum IL-10 and IL-1Ra levels were significantly higher in the febrile seizure patients than in the fever-only control, fever only with a febrile seizure history, and afebrile seizure groups (p < 0.05). The serum IFN-γ and IL-6 levels were significantly higher in the febrile seizure patients than in the afebrile seizure group (p < 0.05). The serum IL-8 levels were higher in the febrile seizure patients than in the fever only controls (p < 0.05). CONCLUSIONS: The serum levels of the IFN-γ, IL-6, and IL-8 pro-inflammatory cytokines and the serum levels of the IL-10 and IL-1Ra anti-inflammatory cytokines were significantly higher in the febrile seizure children. Furthermore, the serum level of IL-1Ra was more increased in the febrile seizure group than in the same patients with only a fever. Our data suggest that increased serum IL-10 and IL-1Ra may play potential roles as anti-inflammatory cytokines in a compensation mechanism that shortens the seizure duration or prevents a febrile seizure attack. Therefore, anti-inflammatory cytokines, including IL-10 and IL-1Ra, have potential as therapeutic targets for the prevention of seizures and nervous system development of children.

Expression and functional role of metallothioneins I and II in the spinal cord in inflammatory and neuropathic pain models.

In this study, the expression and functional role of metallothioneins I and II (MT-I/II) were evaluated in the spinal cord in rat models of inflammatory and neuropathic pain. Complete Freund's adjuvant (CFA) injection into the hindpaw induced an increase in MT-I/II protein expression in bilateral dorsal and ventral horns throughout the spinal cord, while chronic constriction injury (CCI) of the sciatic nerve induced an increase in MT-I/II expression in the ipsilateral dorsal and ventral horns of the lower lumbar spinal cord. Increased MT-I/II immunoreactivity was predominantly localized to vascular endothelial cells. CFA injection- and CCI-induced MT-I/II expression was inhibited by intrathecal administration of MT-I siRNA. Treatment with MT-I siRNA before CFA injection or at early time points after CCI resulted in a significant attenuation of mechanical allodynia and thermal hyperalgesia, while treatment at later time points had no effect on established pain behaviors. Our results suggest that endogenous MT-I/II might play an important role in the pathogenesis of pain behaviors, participating in the initiation of inflammatory and neuropathic pain rather than in their maintenance.