CYTOKINE EXPRESSION OF MACROPHAGES IN HIV-1-ASSOCIATED VACUOLAR MYELOPATHY

Macrophages are frequently present within the periaxonal and intramyel inic vacuoles that are located primarily in the posterior and lateral funiculi of the thoracic spinal cord in HIV-associated vacuolar myelop athy. But the role of these macrophages in the formation of the vacuol es is unclear. One hypothesis is that cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor (TNF)-alpha, are produced locally by macrophages and have toxic effects on myelin or oligodendrocytes. The resulting myelin damage eventually culminates in the removal of myeli n by macrophages and vacuole formation. We studied thoracic spinal cor d specimens taken at autopsy from HIV-positive (+) and HIV-negative in dividuals. The predominant mononuclear cells present in HIV+ spinal co rds are macrophages. They are located primarily in the posterior and l ateral funiculi regardless of the presence or absence of vacuolar myel opathy. Macrophages and microglia are more frequent in HIV+ than HIV-n egative individuals and these cells frequently stain for class I and c lass II antigens, IL-1, and TNF-alpha. Activated macrophages positive for IL-1 and TNF-alpha are greatly increased in the posterior and late ral funiculi of HIV+ individuals with and without vacuolar myelopathy, suggesting they are present prior to the development of vacuoles. Cyt okines, such as TNF-alpha, may be toxic for myelin or oligodendrocytes , leading to myelin damage and removal by macrophages and vacuole form ation.