The Interleukin-1 Balance During Encephalitis Is Associated With Clinical Severity, Blood-Brain Barrier Permeability, Neuroimaging Changes, and Disease Outcome

J Infect Dis. 2016 May 15;213(10):1651-60. doi: 10.1093/infdis/jiv771. Epub 2015 Dec 27.


Background: Encephalitis is parenchymal brain inflammation, commonly due to herpes simplex virus (HSV). Key host inflammatory mediators and their relationship to blood-brain barrier (BBB) permeability, neuroimaging changes, and disease outcome are poorly understood.

Methods: We measured levels of 38 mediators in serum (n = 78) and cerebrospinal fluid (n = 37) specimens from patients with encephalitis, including 17 with disease due to HSV infection. Outcome measures were Glasgow coma and outcome scores; CSF to serum albumin ratio, reflecting BBB permeability; and, in patients with HSV infection, magnetic resonance imaging-based temporal lobe volume.

Results: Serum interleukin 1 receptor antagonist (IL-1RA) levels were elevated in patients with a good outcome (P= .004). Among patients infected with HSV, the ratio of CSF IL-1β to IL-1RA was associated with a worse outcome (P= .009); a ratio of ≥0.55 pg/mL had high specificity and sensitivity for a poor outcome (100% and 83%;P= .015). Temporal lobe volume had a negative correlation with serum IL-1RA level (P= .012) and a positive correlation with serum IL-1α level (P= .0003) and CSF IL-1β level (P= .007). A normal coma score was associated with an elevated interleukin 10 (IL-10) level in serum specimens from HSV-infected patients (P= .007) and CSF specimens from all patients (P= .016); the IL-10 level correlated inversely with BBB permeability (P= .005).

Conclusions: A proinflammatory cytokine response is associated with greater clinical severity, BBB permeability, and neuroimaging damage during encephalitis. IL-1 antagonists should be investigated as adjunctive treatment in encephalitis.

Keywords: blood-brain barrier; chemokine; cytokine; encephalitis; herpes simplex.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albumins / cerebrospinal fluid
  • Blood-Brain Barrier*
  • Capillary Permeability*
  • Cohort Studies
  • Encephalitis, Herpes Simplex / blood
  • Encephalitis, Herpes Simplex / cerebrospinal fluid
  • Encephalitis, Herpes Simplex / immunology*
  • England
  • Glasgow Coma Scale
  • Humans
  • Inflammation Mediators* / blood
  • Inflammation Mediators* / cerebrospinal fluid
  • Interleukin 1 Receptor Antagonist Protein / blood
  • Interleukin 1 Receptor Antagonist Protein / cerebrospinal fluid
  • Interleukin-1 / blood
  • Interleukin-1 / cerebrospinal fluid
  • Interleukin-1 / metabolism*
  • Interleukin-10 / blood
  • Interleukin-10 / cerebrospinal fluid
  • Interleukin-1beta / blood
  • Interleukin-1beta / cerebrospinal fluid
  • Magnetic Resonance Imaging
  • Neuroimaging
  • Prospective Studies
  • Serum Albumin / analysis
  • Simplexvirus / immunology
  • Temporal Lobe / pathology


  • Albumins
  • IL10 protein, human
  • Inflammation Mediators
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Interleukin-1beta
  • Serum Albumin
  • Interleukin-10