Cytokines and other markers of intrathecal immune response in patients with herpes simplex encephalitis

Sequential samples of serum and cerebrospinal fluid (CSF), from 9 patients with herpes simplex encephalitis (HSE), were analyzed for cytokines and soluble cytokine receptors. The response to herpes simplex virus was characterized by a vigorous compartmentalized immune response. The intrathecal response comprised three different phases: an acute stage (first week of illness), characterized by elevated CSF levels of interleukin (IL)-6 and interferon-gamma; an early convalescence stage (weeks 2-6 after onset of disease), associated with peaking levels of tumor necrosis factor-alpha and late markers of the specific T cell-mediated immune response, soluble IL-2 receptor, and soluble CD8 antigen (sCD8); and finally, a late convalescence stage, lasting months to years and associated with persistently increased levels of sCD8 in particular. These findings show the compartmentalization and kinetics of the inflammatory response in HSE and demonstrate persistence of the intrathecal inflammatory process, which may have implications for antiviral and antiinflammatory therapy.