The case for immunomodulatory approaches in treating HSV encephalitis.

HSV encephalitis (HSE) is the most prevalent sporadic viral encephalitis. Although safe and effective antiviral therapies and greatly improved noninvasive diagnostic procedures have significantly improved outcomes, mortality (~20%) and debilitating neurological sequelae in survivors remain unacceptably high. An encouraging new development is that the focus is now shifting away from the virus exclusively, to include consideration of the host immune response to infection in the pathology underlying development of HSE. In this article, the authors discuss results from recent studies in experimental mouse models, as well as clinical reports that demonstrate a role for exaggerated host inflammatory responses in the brain in the development of HSE that is motivating researchers and clinicians to consider new therapeutic approaches for treating HSE. The authors also discuss results from a few studies that have shown that immunomodulatory drugs can be highly protective against HSE, which supports a role for deleterious host inflammatory responses in HSE. The impressive outcomes of some immunomodulatory approaches in mouse models of HSE emphasize the urgent need for clinical trials to rigorously evaluate combination antiviral and immunomodulatory therapy in comparison with standard antiviral therapy for treatment of HSE, and support for such an initiative is gaining momentum.