Cellular localization of tumor necrosis factor mRNA in neurological tissue from HIV-infected patients by combined reverse transcriptase/polymerase chain reaction in situ hybridization and immunohistochemistry

HIV-induced neurological disease is postulated to be caused by indirect mechanisms. Tumor necrosis factor (TNF)α is increased in the brains in human immunodeficiency virus (HIV)-associated dementia and in the spinal cord in vacuolar myelopathy and may play a pathogenetic role in these diseases. Microglia, astrocytes and infiltrating macrophages can be induced to produce TNFα and each has been identified as a source of TNFα in neurological disease. Reverse transcriptase synthesis of cDNA and polymerase chain reaction amplification of the cDNA was combined with immunocytochemistry to identify the cellular source of TNFα in HIV-induced neurological disease. Cells positive for TNFα mRNA were more abundant in white matter than gray matter of the brain from demented individuals. TNFα mRNA-positive cells in brains and spinal cords were almost exclusively macrophage-lineage cells. Only rare TNFα mRNA-positive cells were astrocytes. We conclude that macrophage-lineage cells are the primary source of elevated central nervous system TNFα mRNA in providing further evidence that macrophage activation is an important element in the pathogenesis of HIV-associated neurological disease.