Cytokine profiles in children with PCR-confirmed HHV-6 infection according to seizure occurrence

Although cytokines are contributors to febrile seizures, previous studies have largely involved pathogen-heterogeneous populations. Human herpesvirus 6 (HHV-6) is a common cause of febrile seizures and is useful for studying pathogen-specific inflammatory responses.

This retrospective study included children with polymerase chain reaction-confirmed HHV-6 infection using stored plasma samples obtained within 72 h of hospital presentation, classified according to seizure status. Plasma cytokine levels were measured using a multiplex immunoassay. Multivariable linear regression was used to identify the cytokines associated with seizures, with Benjamini-Hochberg false discovery rate (FDR) correction across 15 cytokines. Correlations between cytokine levels and hematologic parameters were evaluated. Cerebrospinal fluid (CSF)-to-plasma cytokine ratios were analyzed.

Sixty patients were included (37, without seizures; 23, seizures), with no significant differences in baseline characteristics between the groups. Plasma interleukin-8 (IL-8) showed an association with seizures (adjusted fold change 1.84, p = 0.03), but this association did not remain statistically significant after FDR correction (q = 0.45). Inverse correlations between IL-8 (and to a lesser extent macrophage inflammatory protein-1 alpha) and neutrophil and platelet counts were observed in the non-seizure group only. In the paired analyses (n = 8), the CSF-to-plasma ratios of IL-8 and monocyte chemoattractant protein-1 exceeded 1.0, with a trend toward higher IL-8 ratios in the seizure group after adjusting for age.

Although exploratory, findings from this pathogen-homogeneous cohort suggest that IL-8 is a candidate cytokine associated with both seizure occurrence and an altered relationship with neutrophil and platelet counts, warranting further study.