1. Unifying hypothesis for the pathogenesis of HIV-associated dementia complex, vacuolar myelopathy, and sensory neuropathy.
- Author
-
Tyor WR, Wesselingh SL, Griffin JW, McArthur JC, and Griffin DE
- Subjects
- Humans, Spinal Cord ultrastructure, Vacuoles ultrastructure, AIDS Dementia Complex etiology, Acquired Immunodeficiency Syndrome complications, Peripheral Nervous System Diseases etiology, Spinal Cord Diseases etiology
- Abstract
Neurological diseases associated with HIV infection include dementia, vacuolar myelopathy, and sensory neuropathy. Although in vitro studies suggest that other nervous system cell types could harbor HIV, immunohistochemical and in situ hybridization studies have indicated that only macrophages/microglia are significantly infected in the central nervous system. In the peripheral nervous system, even HIV-infected macrophages are rare. Therefore, theories regarding the pathogenesis of HIV-associated neurologic disorders have centered around the elaboration of substances that may be toxic to neurons, oligodendrocytes or myelin. These potential toxins include HIV proteins, cellular metabolites, and cytokines. In this review we present evidence that there are large numbers of macrophages/microglia present in the nervous system of patients with these diseases and that they produce tumor necrosis factor (TNF)-alpha. The large increase in macrophage activity late in HIV infection may be due to the diminution in production by CD4-positive T cells of cytokines such as interleukin (IL)-4 and IL-10 which are inhibitors of macrophage activities. We hypothesize that HIV-associated dementia complex, vacuolar myelopathy, and sensory neuropathy are directly or indirectly related to the increased numbers of macrophages found in brain, spinal cord, and peripheral nerve. Future therapies may be directed towards inhibition of macrophage functions.
- Published
- 1995