Interleukin-10 is associated with resistance to febrile seizures: Genetic association and experimental animal studies

Yoshito Ishizaki, Ryutaro Kira, Mitsumasa Fukuda, Hiroyuki Torisu, Yasunari Sakai, Masafumi Sanefuji, Naoko Yukaya, Toshiro Hara

Research output: Contribution to journalArticle

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Abstract

Purpose: Febrile seizures (FS) are the most common form of childhood convulsions. Many reports have shown that a proinflammatory cytokine, interleukin-1 (IL-1) β, may have a facilitatory effect on the development of FS. We have previously shown that the IL1B -511C/T single nucleotide polymorphism (SNP) is associated with simple FS of sporadic occurrence. The balance between pro- and antiinflammatory cytokines influences the regulation of infections and could, therefore, play a role in the pathogenesis of FS. Here, to determine whether pro- and antiinflammatory cytokine genes are responsible for the susceptibility to FS, we have performed an association study on functional SNPs of cytokine genes in FS patients and controls. Methods: The promoter SNPs of four inflammatory cytokine genes (IL6 -572C/G, IL8 -251A/T, IL10 -592A/C and TNFA -1037C/T) were examined in 249 patients with FS (186 simple and 63 complex FS) and 225 controls. Because the IL10 -592 SNP showed a positive association with FS, two additional SNPs (IL10 -1082A/G and -819T/C) were subjected to haplotype analysis. Furthermore, we examined the in vivo role of IL-10 in hyperthermia-induced seizures using immature animal models. Results: The frequencies of the IL10 -592C allele and -1082A/-819C/-592C haplotype were significantly decreased in FS as compared with in controls (p = 0.014 and 0.013, respectively). The seizure threshold temperature in the IL-10-administered rats was significantly higher than that in the saline-treated control ones (p = 0.027). Conclusions: The present study suggests that IL-10 is genetically associated with FS and, contrary to IL-1β, confers resistance to FS.

Original languageEnglish
Pages (from-to)761-767
Number of pages7
JournalEpilepsia
Volume50
Issue number4
DOIs
Publication statusPublished - Apr 1 2009

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Febrile Seizures
Interleukin-10
Single Nucleotide Polymorphism
Cytokines
Seizures
Interleukin-1
Haplotypes
Anti-Inflammatory Agents
Genes
Induced Hyperthermia
Interleukin-8
Interleukin-6
Animal Models

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

Cite this

Interleukin-10 is associated with resistance to febrile seizures : Genetic association and experimental animal studies. / Ishizaki, Yoshito; Kira, Ryutaro; Fukuda, Mitsumasa; Torisu, Hiroyuki; Sakai, Yasunari; Sanefuji, Masafumi; Yukaya, Naoko; Hara, Toshiro.

In: Epilepsia, Vol. 50, No. 4, 01.04.2009, p. 761-767.

Research output: Contribution to journalArticle

Ishizaki, Yoshito ; Kira, Ryutaro ; Fukuda, Mitsumasa ; Torisu, Hiroyuki ; Sakai, Yasunari ; Sanefuji, Masafumi ; Yukaya, Naoko ; Hara, Toshiro. / Interleukin-10 is associated with resistance to febrile seizures : Genetic association and experimental animal studies. In: Epilepsia. 2009 ; Vol. 50, No. 4. pp. 761-767.
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T1 - Interleukin-10 is associated with resistance to febrile seizures

T2 - Genetic association and experimental animal studies

AU - Ishizaki, Yoshito

AU - Kira, Ryutaro

AU - Fukuda, Mitsumasa

AU - Torisu, Hiroyuki

AU - Sakai, Yasunari

AU - Sanefuji, Masafumi

AU - Yukaya, Naoko

AU - Hara, Toshiro

PY - 2009/4/1

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N2 - Purpose: Febrile seizures (FS) are the most common form of childhood convulsions. Many reports have shown that a proinflammatory cytokine, interleukin-1 (IL-1) β, may have a facilitatory effect on the development of FS. We have previously shown that the IL1B -511C/T single nucleotide polymorphism (SNP) is associated with simple FS of sporadic occurrence. The balance between pro- and antiinflammatory cytokines influences the regulation of infections and could, therefore, play a role in the pathogenesis of FS. Here, to determine whether pro- and antiinflammatory cytokine genes are responsible for the susceptibility to FS, we have performed an association study on functional SNPs of cytokine genes in FS patients and controls. Methods: The promoter SNPs of four inflammatory cytokine genes (IL6 -572C/G, IL8 -251A/T, IL10 -592A/C and TNFA -1037C/T) were examined in 249 patients with FS (186 simple and 63 complex FS) and 225 controls. Because the IL10 -592 SNP showed a positive association with FS, two additional SNPs (IL10 -1082A/G and -819T/C) were subjected to haplotype analysis. Furthermore, we examined the in vivo role of IL-10 in hyperthermia-induced seizures using immature animal models. Results: The frequencies of the IL10 -592C allele and -1082A/-819C/-592C haplotype were significantly decreased in FS as compared with in controls (p = 0.014 and 0.013, respectively). The seizure threshold temperature in the IL-10-administered rats was significantly higher than that in the saline-treated control ones (p = 0.027). Conclusions: The present study suggests that IL-10 is genetically associated with FS and, contrary to IL-1β, confers resistance to FS.

AB - Purpose: Febrile seizures (FS) are the most common form of childhood convulsions. Many reports have shown that a proinflammatory cytokine, interleukin-1 (IL-1) β, may have a facilitatory effect on the development of FS. We have previously shown that the IL1B -511C/T single nucleotide polymorphism (SNP) is associated with simple FS of sporadic occurrence. The balance between pro- and antiinflammatory cytokines influences the regulation of infections and could, therefore, play a role in the pathogenesis of FS. Here, to determine whether pro- and antiinflammatory cytokine genes are responsible for the susceptibility to FS, we have performed an association study on functional SNPs of cytokine genes in FS patients and controls. Methods: The promoter SNPs of four inflammatory cytokine genes (IL6 -572C/G, IL8 -251A/T, IL10 -592A/C and TNFA -1037C/T) were examined in 249 patients with FS (186 simple and 63 complex FS) and 225 controls. Because the IL10 -592 SNP showed a positive association with FS, two additional SNPs (IL10 -1082A/G and -819T/C) were subjected to haplotype analysis. Furthermore, we examined the in vivo role of IL-10 in hyperthermia-induced seizures using immature animal models. Results: The frequencies of the IL10 -592C allele and -1082A/-819C/-592C haplotype were significantly decreased in FS as compared with in controls (p = 0.014 and 0.013, respectively). The seizure threshold temperature in the IL-10-administered rats was significantly higher than that in the saline-treated control ones (p = 0.027). Conclusions: The present study suggests that IL-10 is genetically associated with FS and, contrary to IL-1β, confers resistance to FS.

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