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A potential role for interferon-alpha in the pathogenesis of HIV-associated dementia

M B Rho1, S Wesselingh, J D Glass

  • 1Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21218, USA.

Brain, Behavior, and Immunity
|December 1, 1995
PubMed

Insights

Elevated interferon-alpha (IFN-alpha) in cerebrospinal fluid (CSF) is linked to cognitive decline in HIV-associated dementia. This suggests brain cells produce IFN-alpha, contributing to HIV dementia pathogenesis.

Area of Science:

  • Neuroscience
  • Immunology
  • Virology

Background:

  • Elevated cerebrospinal fluid (CSF) interferon-alpha (IFN-alpha) is associated with cognitive dysfunction in patients on IFN-alpha therapy and those with systemic lupus erythematosus.
  • Human immunodeficiency virus (HIV) infection can lead to neurological complications, including HIV-associated dementia (HAD).

Purpose of the Study:

  • To investigate the association between CSF and blood IFN-alpha levels and cognitive function in HIV-positive individuals.
  • To determine if IFN-alpha is produced within the brain in HIV-associated dementia.

Main Methods:

  • Measurement of IFN-alpha levels in CSF and blood using ELISA in HIV-positive patients with and without dementia, and HIV-negative controls.
  • Immunocytochemical staining of brain tissue to identify IFN-alpha-producing cells.
  • Detection of IFN-alpha mRNA in brain tissue using reverse transcriptase-polymerase chain reaction (RT-PCR).

Main Results:

  • CSF IFN-alpha levels were significantly elevated in HIV-positive patients with dementia compared to those without dementia and HIV-negative controls.
  • A trend was observed correlating increased CSF IFN-alpha with higher Memorial Sloan Kettering scores, suggesting a link to neurocognitive dysfunction in AIDS.
  • IFN-alpha-positive macrophages and astrocytes were identified in the frontal cortex and white matter of brains from patients with HAD.
  • IFN-alpha mRNA was detected in brain tissue, indicating local production by intrinsic brain cells.

Conclusions:

  • Significantly increased CSF IFN-alpha levels in HIV-associated dementia are likely derived from intrinsic brain cells, such as macrophages and astrocytes.
  • Increased local production of IFN-alpha during HIV infection may play a role in the pathogenesis of HIV-associated dementia.
  • These findings highlight the potential involvement of neuroinflammation mediated by IFN-alpha in HIV-induced cognitive impairment.

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