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

研究成果: Contribution to journalArticle査読

40 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)761-767
ページ数7
ジャーナルEpilepsia
50
4
DOI
出版ステータス出版済み - 4 2009

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

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