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.
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.
Authors: Anne A Kan; Wilco de Jager; Marina de Wit; Cobi Heijnen; Mirjam van Zuiden; Cyrill Ferrier; Peter van Rijen; Peter Gosselaar; Ellen Hessel; Onno van Nieuwenhuizen; Pierre N E de Graan Journal: J Neuroinflammation Date: 2012-08-30 Impact factor: 8.322
Authors: Bart C Jongbloets; Koen L I van Gassen; Anne A Kan; Anneke H O Olde Engberink; Marina de Wit; Inge G Wolterink-Donselaar; Marian J A Groot Koerkamp; Onno van Nieuwenhuizen; Frank C P Holstege; Pierre N E de Graan Journal: PLoS One Date: 2015-12-18 Impact factor: 3.240
Authors: Symon M Kariuki; Kirk Rockett; Taane G Clark; Hugh Reyburn; Tsiri Agbenyega; Terrie E Taylor; Gretchen L Birbeck; Thomas N Williams; Charles R J C Newton Journal: Epilepsia Date: 2013-04-24 Impact factor: 5.864