Increased plasma levels of pro- and anti-inflammatory cytokines in patients with febrile seizures

Purpose: Pro- and antiinflammatory cytokines regulate the febrile response during infection. Febrile seizures (FSs) conversely are associated with rapid onset of high fever. Activation of the cytokine network has been shown in previous studies of FSs and cytokines. In this study, the association between cytokines and FSs was further investigated. Methods: Interleukin-1beta (IL-1beta), interleukin-1 receptor antagonist (IL-IRA), interleukin-6 (IL-6), interleukin-10, and tumor necrosis factor-a plasma levels were measured with enzyme-linked immunosorbent assay in 55 children with FSs and in 20 age-matched febrile controls immediately on arrival at the hospital. Cerebrospinal fluid cytokine levels also were measured in 16 FS children. Results: The plasma IL-1RA/IL-1beta ratio (mean, 2,133 vs. 119; median, 790 vs. 105: p < 0.0001) and plasma IL-6 (mean, 41.7 pg/ml vs. 16.1 pg/ml: median, 19.6 pg/ml vs. 10.5 pg/ml; p = 0.005) were significantly higher in FS patients compared with control children. Logistic regression analysis was used to find the most significant predisposing factors for FSs. In this analysis, the high plasma IL-1RA/IL-1 beta ratio was the most significant factor connected to FSs (OR, 41.5; 95% CI, 4.9-352.8), but high plasma IL-6 also was significantly associated with FSs (OR, 5.3; 95% CI, 1.4-20.3). Conclusions: Present results support the hypothesis that the cytokine network is activated and could have a role in the pathogenesis of FS.