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Epilepsia. 2009 Apr;50(4):761-7. doi: 10.1111/j.1528-1167.2008.01861.x. Epub 2008 Dec 4.

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

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1
Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. ishizaki@pediatr.med.kyushu-u.ac.jp

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) 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.

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-1beta, confers resistance to FS.

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