title: The Interleukin-1 Balance During Encephalitis Is Associated With Clinical Severity, Blood-Brain Barrier Permeability, Neuroimaging Changes, and Disease Outcome.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Institute of Infection and Global Health Health Protection Research Unit in Emerging and Zoonotic Infections, National Institute for Health Research, University of Liverpool Walton Centre National Health Service (NHS) Foundation Trust.
authors.forename: Benedict Daniel
authors.initials: BD
authors.lastname: Michael
authors.affiliation: Institute of Infection and Global Health Health Protection Research Unit in Emerging and Zoonotic Infections, National Institute for Health Research, University of Liverpool Alderhey Children's NHS Foundation Trust, Liverpool.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Griffiths
authors.affiliation: Public Health England, London.
authors.forename: Julia
authors.initials: J
authors.lastname: Granerod
authors.affiliation: Public Health England, London Influenza and Measles Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: David
authors.initials: D
authors.lastname: Brown
authors.affiliation: Walton Centre National Health Service (NHS) Foundation Trust.
authors.forename: Geoff
authors.initials: G
authors.lastname: Keir
authors.affiliation: Institute of Infection and Global Health.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Wnęk
authors.affiliation: Faculty of Medical and Human Sciences, Centre for Imaging Sciences, Institute of Population Health, University of Manchester.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Cox
authors.affiliation: Faculty of Medical and Human Sciences, Centre for Imaging Sciences, Institute of Population Health, University of Manchester.
authors.forename: Rishma
authors.initials: R
authors.lastname: Vidyasagar
authors.affiliation: Vaccine Evaluation Unit, Public Health England, Manchester, United Kingdom.
authors.forename: Ray
authors.initials: R
authors.lastname: Borrow
authors.affiliation: Faculty of Medical and Human Sciences, Centre for Imaging Sciences, Institute of Population Health, University of Manchester.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Parkes
authors.affiliation: Institute of Infection and Global Health Health Protection Research Unit in Emerging and Zoonotic Infections, National Institute for Health Research, University of Liverpool Walton Centre National Health Service (NHS) Foundation Trust.
authors.forename: Tom
authors.initials: T
authors.lastname: Solomon
mesh_terms: D000418:Albumins / Q000134:cerebrospinal fluid; D001812:Blood-Brain Barrier; D002199:Capillary Permeability; D015331:Cohort Studies; D020803:Encephalitis, Herpes Simplex / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D004739:England; D015600:Glasgow Coma Scale; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood / Q000134:cerebrospinal fluid; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood / Q000134:cerebrospinal fluid; D007375:Interleukin-1 / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D016753:Interleukin-10 / Q000097:blood / Q000134:cerebrospinal fluid; D053583:Interleukin-1beta / Q000097:blood / Q000134:cerebrospinal fluid; D008279:Magnetic Resonance Imaging; D059906:Neuroimaging; D011446:Prospective Studies; D012709:Serum Albumin / Q000032:analysis; D018139:Simplexvirus / Q000276:immunology; D013702:Temporal Lobe / Q000473:pathology
chemical_list: D000418:Albumins; C508609:IL10 protein, human; D018836:Inflammation Mediators; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D053583:Interleukin-1beta; D012709:Serum Albumin; D016753:Interleukin-10
keywords: blood-brain barrier; chemokine; cytokine; encephalitis; herpes simplex