Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 213, Issue 10, Pages 1651-1660Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiv771
Keywords
encephalitis; cytokine; chemokine; herpes simplex; blood-brain barrier
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Funding
- laboratory team at the Vaccine Evaluation Unit, Public Health England, Manchester, United Kingdom
- NIHR, United Kingdom
- NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Liverpool, United Kingdom
- MRC
- Academy of Medical Sciences (AMS) [SGL015\\1016] Funding Source: researchfish
- 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
- MRC [G116/194, MC_PC_15096] Funding Source: UKRI
- 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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