Expression of HIV‐1 and interleukin‐6 in lumbosacral dorsal root ganglia of patients with AIDS

Abstract

We examined the immunopathology and the expression of human immunodeficiency virus type 1 (HIV-1) in lumbosacral dorsal root ganglia (DRGs) from 16 patients with acquired immunodeficiency syndrome (AIDS) and 10 HIV-1-seronegative controls. Using in situ hybridization, we detected HIV-1 RNA in a few perivascular cells in DRGs from five of 16 AIDS patients (31%). In addition, using polymerase chain reaction, we detected HIV-1 DNA more frequently in DRGs from four of five AIDS patients (80%) examined. We detected interleukin-6 (IL-6) immunoreactivity in endothelial cells in DRGs from seven of 16 AIDS patients (44%) but from none of 10 HIV-1-seronegative controls (0%). We found more nodules of Nageotte, CD8+ T lymphocytes, and intercellular adhesion molecule-1 (ICAM-1)-positive endothelial cells and mononuclear cells in DRGs from AIDS patients than in DRGs from controls. Increased numbers of nodules of Nageotte in DRGs of AIDS patients were associated with detection of HIV-1 RNA by in situ hybridization and detection of IL-6 by immunohistochemistry. We conclude that low levels of replication of HIV-1, through cytotoxic T lymphocytes or expression of cytokines, may play a role in the subclinical degeneration of sensory neurons frequently observed in DRGs of AIDS patients.

Neuromuscular complications in HIV

“…These findings suggest that there is a common indirect cytotoxic mechanism for both DSP and vacuolar myelopathy, which leads to myelin and axonal damage [12]. The presence of Nageotte nodules (cellular proliferations comprised mainly of lymphocytes and activated macrophages) in DRG reinforces the theory of cytokine-mediated indirect mechanisms in HIV neuropathogenesis [13][14][15][16].…”

HIV-1 infected and immune competent mononuclear phagocytes induce quantitative alterations in neuronal dendritic arbor: Relevance for HIV-1-associated dementia

“…This disruption enhances the transendothelial migration of monocytes into the brain which increases the viral reservoir and inevitably effects cognitive, behavioral and motor impairments in HAD. Neuronal death can accompany increased viral replication, particularly in the cortex, the limbic system, and the basal ganglia (Weis et al, 1993;Wiley et al, 1991;Yoshioka et al, 1994). Interestingly, the absolute numbers of immunologically competent brain macrophages and microglia in the CNS, and not the levels of viral expression, appear to be the best predictor of neurologic impairments (Asare et al, 1996;Glass et al, 1995;Glass et al, 1993).…”

HIV Associated Neuropathies

“…The presence of HIV-infected perivascular macrophages has been shown in the DRG of patients with and without DSP. These studies demonstrated the presence of HIV proviral DNA, mRNA, p24 antigen in these cells [28][29][30][31]. Another consistent neuropathological abnormality in the DRG appears to be the presence of activated macrophages, which express MHC antigens and pro-inflammatory cytokines [4, 29,31].…”