Local cytokine responses during acute and chronic viral infections of the central nervous system

The ideal immune response generated during viral infection of the brain is one that clears virus but does not disrupt neuronal function. A cytokine response skewed towards the type 2 spectrum T cell cytokines with increased antibody production and decreased cell-mediated immunity and cytotoxicity may be optimal for survival of neurons and the host if it is effective in clearing the pathogen. We have studied cytokine responses to two different types of viral infection of the central nervous system: acute encephalitis associated with Sindbis virus infection of neurons and progressive dementia associated with human immunodeficiency virus infection of microglia. The cytokine response to acute Sindbis virus-induced encephalitis features early and prolonged production of IL-4 and IL-10 and complete recovery. The cytokine response to human immunodeficiency virus-associated dementia features increased TNF and undetectable IL-4 and progressive neuronal dysfunction. These observations support the hypothesis that the optimal array of cytokines in the brain are type 2 and promote local antibody production within the central nervous system.