TUMOR-NECROSIS-FACTOR-ALPHA, MICROGLIA AND ASTROCYTES IN AIDS DEMENTIA COMPLEX

The pathogenesis of HIV-associated cognitive changes is poorly underst ood. Cytokines such as tumor necrosis factor-alpha (TNF-alpha) have be en postulated to contribute to the mechanism of the neurological compl ications of HIV infection. One of the effects of TNF-alpha is to induc e astrocyte proliferation in vitro, The purpose of this study was to l ook for a correlation between the expression of TNF-alpha, astrogliosi s and the degree of cognitive impairment in 12 prospectively assessed AIDS cases without focal brain lesion, 8 of whom were demented. They w ere compared with 6 control patients without neurological disease. Neu ropathological examination showed myelin pallor in 5 of the 8 demented patients. TNF-alpha expression was detected by immunohistochemistry i n the midfrontal cortex, subcortical and deep white matter, and basal ganglia. Not only perivascular macrophages but also some microglial an d endothelial cells were labeled. Most TNF-alpha-positive cells were i n close contact with glial fibrillary acidic protein-positive astrocyt es. They were more numerous than gp41-positive cells. Their density in creased with increasing cognitive impairment and in parallel to the as trogliosis in the frontal cortex, basal ganglia and deep white matter. These findings further support the hypotheses that lesions of the dee p white matter, driven by TNF-alpha, are associated with cognitive alt eration, and that indirect effects of HIV infection in the brain parti cipate in the development of HIV-associated dementia through a diffuse immune activation, mediated by cytokines.