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

Abstract

SUMMARYPurpose: Febrile seizures (FS) are the most common form of childhood convulsions. Many reports have shown that a proinflammatory cytokine, interleukin-1 (IL-1) b, 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 proand 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-1b, confers resistance to FS.

Analysis of Plasma Multiplex Cytokines for Children With Febrile Seizures and Severe Acute Encephalitis

“…8 Interleukin-10 is genetically associated with febrile seizures, and the seizure threshold temperature in interleukin-10-administered rats has been shown to be significantly higher than that in saline-treated controls resistance to seizures. 9 Of all the studied cytokines, only interleukin-6 was significantly correlated with febrile seizures in multivariate analysis. Interleukin-6 has been shown to exert neurotrophic 10-11 and neuroprotective effects.…”

Association of TGFB, but not IL10, single nucleotide polymorphisms with febrile seizures

“…Straussberg et al have shown increased lipopolysaccharide-induced IL-10 production by peripheral blood mononuclear cells from children with a history of FS [14]. Ishizaki et al demonstrated an association between the IL-10 gene and resistance to FS [34]. In contrast, Virta et al have reported that no difference in plasma IL-10 level was found between children with and without FS [35].…”

Pathophysiologie des Fieberkrampfes

“…Auch die alleinige Gabe hoher Interleukindosen kann Anfälle auslösen, und bei Mäusen, die den Rezeptor für In terleukin1β nicht besitzen, ist die hyper thermiebedingte Auslösung von Anfäl len erschwert [7]. Bei anderen Interleu kintypen wurden jedoch auch entgegen gesetzte Effekte gefunden: Die Schwel le für Hyperthermieanfälle wurde in Rat ten nach Interleukin10Gabe erhöht [12], und Interleukin6 verminderte das Auf treten, verlängerte das Interval bis zum Auftreten und verkürzte die Dauer epi leptiformer Anfälle, die durch Erhöhung der Körpertemperatur bei Ratten ausge löst worden waren [8]. Diese Untersu chungen deuten darauf hin, dass neben der Körpertemperaturerhöhung bei Fie ber körpereigene Substanzen im Allge meinen und das Gleichgewicht der ver schiedenen Interleukine im Besonderen eine zusätzliche Rolle bei der Entstehung von Fieberkrämpfen spielt.…”