Cytokine Levels Fluctuate After Onset of Acute Encephalopathy, Febrile Seizures

Cytokine levels change dynamically from minutes to hours in both acute encephalopathy and febrile seizures.

In children with final diagnoses of acute encephalopathy or febrile seizures, serum cytokine levels changed dynamically, such that the concentrations of several cytokines increased within a few hours after onset and decreased 12 to 24 hours after onset, according to study findings published in the journal BMC Neurology.

Recognizing that the dynamics of changes in cytokine levels have not yet been fully elucidated in children with acute encephalopathy and febrile seizures, researchers sought to explore the time course of serum cytokine concentration changes within 72 hours following onset of either of these 2 neurologic manifestations. They retrospectively measured the cytokine levels in residual serum samples at multiple time points in 7 children in whom the final diagnosis was either febrile seizures or acute encephalopathy.

In the retrospective, observational clinical study, febrile seizure was defined “as a seizure accompanied by fever (temperature ≥100.4°F or 38°C by any method), without central nervous system infection, that occurs in infants and children from 6 months to 14 years of age.” Acute encephalopathy was defined as “an impairment in consciousness of acute onset, with severity of Japan Coma Scale 20 or Glasgow Coma Scale <11, and with duration of 24h or longer according to the Guidelines for the diagnosis and treatment of acute encephalopathy in childhood.”

For the study, researchers measured the levels of 16 different cytokines:

  • interleukin (IL)-1β
  • IL-1 receptor antagonist (IL-1RA), IL-4, IL-5, IL-6, IL-8, IL-10, IL-17
  • eotaxin
  • fibroblast growth factor (FGF)
  • granulocyte colony-stimulating factor (GCSF)
  • interferon gamma (IFN-γ)
  • interferon-inducible protein 10 (IP-10)
  • macrophage chemoattractant protein-1 (MCP-1)
  • macrophage inflammatory protein-1α (MIP-1 α)
  • platelet-derived growth factor-bb (PDGF-bb)

The 7 patients in the study included 4 boys and 3 girls aged 1-9 years. The participants’ final diagnoses were hemorrhagic shock and encephalopathy syndrome (HSES) in 3 children, acute encephalopathy with early biphasic seizures and later reduced diffusion (AESD) in 2 children, and febrile seizures in 2 children.

[T]he results suggested that AE and FS may be neuroinflammatory spectrum disorders associated with fever because cytokine levels increased in all syndromes.

Results of the analysis showed that the levels of 13 of the 16 cytokines appeared to increase immediately following onset and peaked within 12 to 24 hours after onset: IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-17, eotaxin, FGF, GCSF, IFN-γ, IP-10, and MCP-1. No dynamic changes in the levels of the other 3 cytokines — that is, IL-1RA, MIP-1 α, and PDGF-bb — were observed 72 hours after disease onset.

Within 48 hours following disease onset, the levels of some of the cytokines decreased to around control levels: IL-1β, IL-4, IL-5, IL-17, FGF, and IFN-γ. The levels of most of the cytokines seemed to be higher among those with acute encephalopathy, however — in particular, in participants with AESD — compared with those with febrile seizures.

Several limitations of the study warrant mention. The specimens were obtained by random blood sampling, with the sampling time being predetermined. The sample size, however, was too small to demonstrate the exact dynamics of cytokines in different time points. Further, because cytokine levels in patients with acute encephalopathy and febrile seizures were not compared in the study, a future comparative analysis in a larger number of patients is warranted in the future.

The researchers concluded that “Although our study could not differentiate AE [acute encephalopathy] and FS [febrile seizures] by cytokine levels, but the results suggested that AE and FS may be neuroinflammatory spectrum disorders associated with fever because cytokine levels increased in all syndromes.”


Tomioka K, Nishiyama M, Tokumoto S, et al. Time course of serum cytokine level changes within 72 h after onset in children with acute encephalopathy and febrile seizures. BMC Neurol. Published online January 7, 2023. doi:10.1186/s12883-022-03048-8