Elevated serum IL-18 and IL-37 levels and their association with seizure burden in paediatric epilepsy.

BACKGROUND: Neuroinflammation is increasingly recognized as a key contributor to epileptogenesis and epilepsy progression. Interleukin-18 (IL-18), a pro-inflammatory cytokine of the interleukin-1 family, has been implicated in seizure susceptibility, whereas interleukin-37 (IL-37) acts as a natural anti-inflammatory regulator of IL-18 driven response. However, the role of the IL-18/IL-37 axis in paediatric epilepsy remains unclear. OBJECTIVES: The aim of this study was to assess serum IL-18 and IL-37 levels and to examine their associations with seizure burden in paediatric epilepsy. METHODS: A total of 117 children with epilepsy and 53 age- and sex-matched healthy controls were included. Serum concentrations of IL-18 and IL-37 were measured using enzyme-linked immunosorbent assay. IL-18 and IL-37 gene polymorphisms were analyzed by allele-specific polymerase chain reaction. RESULTS: Both IL-18 and IL-37 levels were significantly elevated in patients with epilepsy compared with controls with the highest concentrations observed in children with high seizure frequency (P vs controls: IL-18 p = 0.0022; IL-37 p ≤ 0.0050). A strong positive correlation was observed between IL-18 and IL-37 concentrations (R = 0.75, p < 0.0001). No significant associations were found between cytokine levels and epilepsy duration, time since the last seizure or other clinical parameters. Genetic polymorphisms did not differ significantly between patients and controls. CONCLUSIONS: Our findings suggest that IL-18 and IL-37 are associated with seizure burden and may represent promising candidate biomarkers in paediatric patients with epilepsy. However, these findings should be considered preliminary and warrant confirmation in larger independent longitudinal studies. To our knowledge, this is the first clinical study to assess serum IL-37 concentrations in patients with epilepsy.