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

Abstract

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.