Michael Benedict Daniel, Griffiths Michael J, Granerod Julia, Brown David, Keir Geoff, Wnęk Małgorzata, Cox Daniel J, Vidyasagar Rishma, Borrow Ray, Parkes Laura M, Solomon Tom
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.
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.
J Infect Dis. 2016 May 15;213(10):1651-60. doi: 10.1093/infdis/jiv771. Epub 2015 Dec 27.
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.
脑炎是实质性脑炎症，通常由单纯疱疹病毒（HSV）引起。关键宿主炎症介质及其与血脑屏障（BBB）通透性、神经影像学变化和疾病转归的关系尚不清楚。
我们检测了脑炎患者血清（n = 78）和脑脊液（n = 37）标本中38种介质的水平，其中17例患者的疾病由HSV感染引起。转归指标包括格拉斯哥昏迷评分和转归评分；脑脊液与血清白蛋白比值，反映BBB通透性；对于HSV感染患者，基于磁共振成像的颞叶体积。
预后良好的患者血清白细胞介素1受体拮抗剂（IL-1RA）水平升高（P = .004）。在HSV感染患者中，脑脊液IL-1β与IL-1RA的比值与较差的预后相关（P = .009）；比值≥0.55 pg/mL对不良预后具有高特异性和敏感性（100%和83%；P = .015）。颞叶体积与血清IL-1RA水平呈负相关（P = .012），与血清IL-1α水平呈正相关（P = .0003），与脑脊液IL-1β水平呈正相关（P = .007）。在HSV感染患者的血清标本（P = .007）和所有患者的脑脊液标本（P = .016）中，正常昏迷评分与白细胞介素10（IL-10）水平升高相关；IL-10水平与BBB通透性呈负相关（P = .005）。
促炎细胞因子反应与脑炎期间更高的临床严重程度、BBB通透性和神经影像学损伤相关。应研究IL-1拮抗剂作为脑炎的辅助治疗。
