Serum and cerebrospinal fluid cytokines in children with acute encephalopathy

Brain Dev. 2020 Feb;42(2):185-191. doi: 10.1016/j.braindev.2019.11.002. Epub 2019 Nov 29.

Abstract

Background: The pathogenesis of acute encephalopathy (AE) remains unclear, and a biomarker has not been identified.

Methods: Levels of 49 cytokines and chemokines, including osteopontin (OPN), were measured in serum and cerebrospinal fluid (CSF) of children with AE (n = 17) or febrile convulsion (FC; n = 8; control group). The AE group included acute necrotizing encephalopathy (n = 1), acute encephalopathy with biphasic seizures and late reduced diffusion (AESD; n = 3), clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS; n = 4), and unclassified acute encephalopathy (UCAE; n = 9) that does not meet the criteria of syndrome classification. Five individuals with AE had neurological sequelae or death (poor prognosis), whereas 12 were alive without neurological sequelae (good prognosis).

Results: The CSF:serum ratios of OPN, CC chemokine ligand (CCL)4, and interleukin (IL)-10 were significantly higher in AE than in FC. The CSF levels of macrophage inhibitory factor (MIF) and leukemia inhibitory factor (LIF) were significantly higher in the poor-prognosis group than in the good-prognosis group. The CSF:serum ratios of OPN were significantly higher in AESD and in MERS than in FC. The CSF:serum ratios of MIF and OPN were higher in MERS than in UCAE or FC.

Conclusion: Our results suggest that microglia-related cytokines and chemokines such as OPN, MIF, and LIF could be novel biomarkers of AE, in addition to the previously reported IL-10 and CCL4, and that MIF and LIF may be markers of poor prognosis.

Keywords: Acute encephalopathy; Chemokine; Children; Cytokine; Microglia; Osteopontin.

MeSH terms

  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Brain Diseases / immunology*
  • Brain Diseases / pathology*
  • Chemokines / analysis
  • Chemokines / blood
  • Chemokines / cerebrospinal fluid
  • Child, Preschool
  • Cytokines / analysis*
  • Cytokines / blood
  • Cytokines / cerebrospinal fluid
  • Encephalitis / cerebrospinal fluid
  • Female
  • Humans
  • Infant
  • Intramolecular Oxidoreductases / blood
  • Intramolecular Oxidoreductases / cerebrospinal fluid
  • Leukemia Inhibitory Factor / blood
  • Leukemia Inhibitory Factor / cerebrospinal fluid
  • Macrophage Migration-Inhibitory Factors / blood
  • Macrophage Migration-Inhibitory Factors / cerebrospinal fluid
  • Male
  • Osteopontin / blood
  • Osteopontin / cerebrospinal fluid
  • Seizures / etiology
  • Seizures, Febrile / complications
  • Seizures, Febrile / immunology
  • Seizures, Febrile / pathology

Substances

  • Biomarkers
  • Chemokines
  • Cytokines
  • Leukemia Inhibitory Factor
  • Macrophage Migration-Inhibitory Factors
  • Osteopontin
  • Intramolecular Oxidoreductases
  • MIF protein, human