GLIAL CYTOKINES AS NEUROPATHOGENIC FACTORS IN HIV-INFECTION - PATHOGENIC SIMILARITIES TO ALZHEIMERS-DISEASE

The mechanisms by which human immunodeficiency virus (HIV) infection p rovokes progressive neurodegeneration and dementia in acquired immunod eficiency syndrome (AIDS) remain obscure. In HIV-infected (HIV+) indiv iduals, we found that the brain cells preferentially infected by HIV, viz. the microglia, were abundant, activated, and intensely immunoposi tive for interleukin-1 alpha (IL-1 alpha), an immune response-generate d cytokine that increases the synthesis and processing of beta-amyloid precursor proteins (beta-APP) and promotes proliferation and activati on of astroglia. We also found an increase in the number of activated astroglia expressing elevated levels of S100 beta, a cytokine that inc reases intraneuronal calcium levels and promotes excessive growth of n euronal processes (neurites). These glial changes were accompanied by increased expression of beta-APP immunoreaction product in neurons and overgrown (dystrophic) neurites. In addition, some neurons contained monoclonal antibody Tau-2 immunopositive, neurofibrillary tangle-like structures. Our findings provide evidence that glial activation with i ncreased expression of IL-1 alpha and S100 beta may be important in th e neuropathogenesis of AIDS dementia. We propose that HIV infection pr omotes excessive microglial IL-1 alpha expression with consequent astr ogliosis and increased expression of S100 beta Overexpression of these two cytokines may then be involved in AIDS neuropathogenesis by induc ing gliosis, growth of dystrophic neurites, and calcium-mediated neuro nal cell loss in AIDS.