INDUCTION OF MONOCYTE CHEMOATTRACTANT PROTEIN-1 IN HIV-1 TAT-STIMULATED ASTROCYTES AND ELEVATION IN AIDS DEMENTIA

Activated monocytes release a number of substances, including inflamma tory cytokines and eicosanoids, that are highly toxic to cells of the central nervous system. Because monocytic infiltration of the central nervous system closely correlates with HIV-1-associated dementia, it h as been suggested that monocyte-derived toxins mediate nervous system damage. In the present study, we show that the HIV-1 transactivator pr otein Tat significantly increases astrocytic expression and release of monocyte chemoattractant protein-1 (MCP-1). Astrocytic release of bet a-chemokines, which are relatively less selective for monocytes, inclu ding RANTES, macrophage inflammatory protein-1 alpha, and macrophage i nflammatory protein-1 beta, was not observed. We also show that MCP-1 is expressed in the brains of patients with HIV-1-associated dementia and that, of the beta-chemokines tested, only MCP-1 could be detected in the cerebrospinal fluid of patients with this condition. Together, these data provide a potential link between the presence of HIV-1 in t he brain and the monocytic infiltration that may substantially contrib ute to dementia.