4.7 Article

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

Journal

JOURNAL OF INFECTIOUS DISEASES
Volume 213, Issue 10, Pages 1651-1660

Publisher

OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiv771

Keywords

encephalitis; cytokine; chemokine; herpes simplex; blood-brain barrier

Funding

  1. laboratory team at the Vaccine Evaluation Unit, Public Health England, Manchester, United Kingdom
  2. NIHR, United Kingdom
  3. NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Liverpool, United Kingdom
  4. MRC
  5. Academy of Medical Sciences (AMS) [SGL015\\1016] Funding Source: researchfish
  6. National Institute for Health Research [ACF-2008-07-001, DRF-2010-03-97, NF-SI-0514-10177, CL-2014-07-002, 3546] Funding Source: researchfish
  7. MRC [G116/194, MC_PC_15096] Funding Source: UKRI
  8. National Institutes of Health Research (NIHR) [DRF-2010-03-97] Funding Source: National Institutes of Health Research (NIHR)

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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.aEuro integral 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.aEuro integral 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-1 beta to IL-1RA was associated with a worse outcome (P = .009); a ratio of a parts per thousand yen0.55 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-1 alpha level (P = .0003) and CSF IL-1 beta 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.aEuro integral 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.

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