Immune responses to a commnon virai factor, double-stranded ribonucleic acid (dsRNA), were examined in children with and without a history of febrile seizures (FS), in a study at Saga University, Japan. The blood levels of IL-IB and interferon alpha (IFN-a) cytokines were measured using immunosorbent assays at least 4 weeks after the last febrile episode. IL-IB production was significantly increased in a group of 27 FS patients compared to 18 control children. The levels of IL-1B were 703.7 +/- 1318.4 pg/mL in the FS group cf 94.5 +/- 112.1 pg/mL for controls (P=0.0007). IL-1B production was not significantly different in 9 patients with a single prior FS compared to 18 with multiple FS. IL-IB levels of 3 patients with prolonged FS were 567.1, 206.0, and 20.6 pg/mL, respectively. IFN-a levels were low, often undetectable, in both FS and control groups; controls had significantly higher levels than FS patients (5.5 +/- 4.6 pg/mL cf 1.28 +/- 3.2 pg/mL, P=0.0009). Genotyping of IL-IB and IL-1 receptor antagonist polymorphisms showed no significant differences in allelic distribution among FS patients and controls. IL-IB production was not influenced by genotype. 
COMMENT. Viral infections play a role in the etiology of febrile seizures by more than one possible mechanism: (1) fever per se; (2) a degree of fever that exceeds the individual threshold convulsive temperature; (3) viral neurotropism or viral reactivation; and (4) an elevated cytokine or abnormal immune response to infection. Fever is the essential factor, and the threshold to FS is dependent on the height of the body temperature, not the rate of temperature rise.
Fever induced by infection is regulated by components of the immune response, particularly the proinflammatory cytokines, interleukin-lB (IL-1B), IL-6, and tumor necrosis factor (TNF)-alpha, and the anti-inflammatory cytokine IL-10. Several recent studies have examined the levels of production of various components of the immune response in febrile children with and without seizures, with varying results. Despite some negative findings, most studies favor a cytokine role in febrile seizures. Serum levels of IL-6 and IL-10 are useful indicators of the severity of influenza-associated febrile seizures. [2, 3, 4]