A potential role for interferon-alpha in the pathogenesis of HIV-associated dementia.
Previous studies in patients receiving interferon-alpha (IFN-alpha) therapy and patients with systemic lupus erythematosus have demonstrated that elevated cerebrospinal fluid (CSF) levels of IFN-alpha are associated with cognitive dysfunction. We measured IFN-alpha 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-alpha was significantly elevated in the CSF of HIV-positive patients with dementia compared to those without dementia and controls. An increasing amount of IFN-alpha 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-alpha with neurocognitive dysfunction in AIDS. Immunocytochemical staining of brains demonstrated IFN-alpha-positive macrophages and astrocytes in frontal cortex and white matter and IFN-alpha mRNA was detected by reverse transcriptase-polymerase chain reaction, further indicating that IFN-alpha is made by cells within the brain and suggesting that the significant increases of IFN-alpha 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-alpha during HIV infection may contribute directly or indirectly to the pathogenesis of HIV-associated dementia.
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21218, USA.
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Wesselingh
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Glass
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McArthur
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Choi
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Griffin
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Tyor
D015526:AIDS Dementia Complex / Q000097:blood / Q000134:cerebrospinal fluid / Q000209:etiology* / Q000503:physiopathology; D001253:Astrocytes / Q000378:metabolism; D001483:Base Sequence; D002556:Cerebrospinal Fluid Proteins / Q000032:analysis*; D004797:Enzyme-Linked Immunosorbent Assay; D015658:HIV Infections / Q000097:blood / Q000134:cerebrospinal fluid; D006801:Humans; D016898:Interferon-alpha / Q000097:blood / Q000134:cerebrospinal fluid / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism; D008969:Molecular Sequence Data; D009422:Nervous System Diseases / Q000097:blood / Q000134:cerebrospinal fluid; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D012720:Severity of Illness Index
D002556:Cerebrospinal Fluid Proteins; D016898:Interferon-alpha; D012333:RNA, Messenger