In vivo expression of proinflammatory cytokines in HIV encephalitis: an analysis of 11 autopsy cases

As the pathogenesis of AIDS dementia complex (ADC), cytokines such as TNF-alpha and IL-1 beta have been thought to have toxic effects on CNS cells and induce neuronal cell death. However, many of the discussions have been based on the studies done by in vitro experiments. There are only a few reports which demonstrate proinflammatory cytokines directly in vivo in HIV encephalitis (HIVE) brains, and roles of these cytokines with relation to HIV-1 infection are not yet clarified. In the present study, we examined 11 autopsy cases of HIVE using immunohistochemistry, and explored which cell types expressed these cytokines and whether expression of cytokines was related to viral infection. IL-1 beta was detected in the frontal white matter of all 11 cases where microglial nodules were observed to varying degrees, whereas TNF-alpha was detected in seven cases. IL-1 beta- or TNF-alpha-positive cells were almost restricted to CD68-positive macrophages/microglia and mild expression of these cytokines by astrocytes was observed in two cases with severe HIVE. IL-1 beta was detected in some HIVp24-positive multinucleated giant cells. However, we could not detect TNF-alpha expression in the HIVp24-positive cells, which indicates that IL-1 beta is induced by HIV-1 infection. In conclusion, a macrophage/microglia lineage is the main cell type to release cytokines in HIVE, and IL-1 beta expression by HIV-1-infected cells may be one of the important factors for induction of HIVE. In addition, many non-infected macrophages/microglia as well as some astrocytes express IL-1 beta and TNF-alpha, which might contribute to pathogenesis of ADC.