A potential role for interferon-α in the pathogenesis of hiv-associated dementia

Previous studies in patients receiving interferon-α (IFN-α) therapy and patients with systemic lupus erythematosus have demonstrated that elevated cerebrospinal fluid (CSF) levels of IFN-α are associated with cognitive dysfunction. We measured IFN-α levels in CSF and blood by ELISA in human immunodeficiency virus (HIV)-positive patients with (n = 21) and without (n = 23) dementia and HIV-negative controls (n = 48). IFN-α was significantly elevated in the CSF of HIV-positive patients with dementia compared to those without dementia and controls. An increasing amount of IFN-α in the CSF was correlated with the clinical parameter of increasing Memorial Sloan Kettering scores; although these correlations were not statistically significant, they further suggest an association of increased CSF IFN-α with neurocognitive dysfunction in AIDS. Immunocytochemical staining of brains demonstrated IFN-α-positive macrophages and astrocytes in frontal cortex and white matter and IFN-α mRNA was detected by reverse transcriptase-polymerase chain reaction, further indicating that IFN-α is made by cells within the brain and suggesting that the significant increases of IFN-α protein found in the CSF of patients with HIV-associated dementia complex are derived from intrinsic brain cells such as macrophages and astrocytes. Increased local production of IFN-α during HIV infection may contribute directly or indirectly to the pathogenesis of HIV-associated dementia.