Ishizaki Yoshito, Kira Ryutaro, Fukuda Mitsumasa, Torisu Hiroyuki, Sakai Yasunari, Sanefuji Masafumi, Yukaya Naoko, Hara Toshiro
Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Epilepsia. 2009 Apr;50(4):761-7. doi: 10.1111/j.1528-1167.2008.01861.x. Epub 2008 Dec 4.
Febrile seizures (FS) are the most common form of childhood convulsions. Many reports have shown that a proinflammatory cytokine, interleukin-1 (IL-1) beta, 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.
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.
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).
The present study suggests that IL-10 is genetically associated with FS and, contrary to IL-1beta, confers resistance to FS.
热性惊厥（FS）是儿童惊厥最常见的形式。许多报告表明，促炎细胞因子白细胞介素-1（IL-1）β可能对FS的发生发展具有促进作用。我们之前已经表明，IL1B -511C/T单核苷酸多态性（SNP）与散发性单纯FS相关。促炎和抗炎细胞因子之间的平衡影响感染的调节，因此可能在FS的发病机制中起作用。在此，为了确定促炎和抗炎细胞因子基因是否与FS易感性相关，我们对FS患者和对照中细胞因子基因的功能性SNP进行了关联研究。
在249例FS患者（186例单纯性和63例复杂性FS）和225例对照中检测了四种炎性细胞因子基因（IL6 -572C/G、IL8 -251A/T、IL10 -592A/C和TNFA -1037C/T）的启动子SNP。由于IL10 -592 SNP与FS呈正相关，对另外两个SNP（IL10 -1082A/G和-819T/C）进行了单倍型分析。此外，我们使用未成熟动物模型研究了IL-10在热诱导惊厥中的体内作用。
与对照相比，FS患者中IL10 -592C等位基因和-1082A/-819C/-592C单倍型的频率显著降低（分别为p = 0.014和0.013）。给予IL-10的大鼠的惊厥阈值温度显著高于给予生理盐水的对照大鼠（p = 0.027）。
本研究表明，IL-10与FS存在遗传关联，并且与IL-1β相反，赋予对FS的抗性。
