Cerebrospinal fluid and serum cytokine profiles in severe viral encephalitis with implications for refractory status epilepticus: a retrospective observational study

Front Immunol. 2025 Feb 10:16:1528763. doi: 10.3389/fimmu.2025.1528763. eCollection 2025.

Abstract

Background: To identify new intervention targets, we explored the correlation between cytokines and the development of refractory status epilepticus (RSE) in patients with severe viral encephalitis (SVE).

Methods: We examined the characteristics of 14 cytokines in the cerebrospinal fluid (CSF) and serum, analyzing their correlation with acute symptomatic seizures and prognosis. Furthermore, we conducted a dynamic analysis of differences and correlations in the expression of cytokines among patients with SVE without seizures, those with controlled seizures, and those with RSE.

Results: We included 161 patients with SVE; the incidence of seizures was 55.2%, and the mortality rate was 5.5%. Notably, 18.9% of these patients developed RSE, with a mortality rate of 20%. During the early stage of SVE, CSF interleukin (IL)-6 and IL-8 levels were significantly higher, declining over time and affecting the prognosis. CSF IL-6 and IL-8 levels were significantly elevated in the RSE group compared to patients without seizures and with controlled seizures, decreasing gradually and independently of serum cytokine levels. CSF IL-8 and age were independent risk factors for RSE, with clinical utility.

Conclusions: Patients with SVE exhibit intrathecal cytokine storms, primarily characterized by elevated levels of IL-6 and IL-8, which influence prognosis. The strong and persistent hyperinflammation underscored by CSF IL-6 and IL-8 is associated with the occurrence and development of RSE; thus, CSF IL-8 and age are independent risk factors for SVE with RSE, indicating potential anti-inflammatory intervention targets.

Keywords: cerebrospinal fluid; cytokines; refractory status epilepticus; serum; severe viral encephalitis.

Publication types

  • Observational Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Cytokines* / blood
  • Cytokines* / cerebrospinal fluid
  • Encephalitis, Viral* / blood
  • Encephalitis, Viral* / cerebrospinal fluid
  • Encephalitis, Viral* / complications
  • Encephalitis, Viral* / immunology
  • Encephalitis, Viral* / mortality
  • Female
  • Humans
  • Interleukin-6 / blood
  • Interleukin-6 / cerebrospinal fluid
  • Interleukin-8 / blood
  • Interleukin-8 / cerebrospinal fluid
  • Male
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Status Epilepticus* / blood
  • Status Epilepticus* / cerebrospinal fluid
  • Status Epilepticus* / diagnosis
  • Status Epilepticus* / etiology
  • Young Adult

Substances

  • Cytokines
  • Interleukin-8
  • Interleukin-6
  • Biomarkers