The pathogenesis of the dementia associated with human immunodeficieny virus (HIV) infection is unclear, but has been postulated to be due to indirect effects of HIV infection including the local production of cytokines. To determine which cytokines are produced in the nervous system and to identify and correlations with dementia, cytokine and HIV messenger RNA expression was analyzed by reverse transcriptase‐polymerase chain reaction in the brains from 24 HIV‐ infected patients with and without dementia and 9 HIV uninfected control subjects. Levels of tumor necrosis factor‐α messenger RNA were significantlyhigher and levels of interleukin (IL)‐4 messenenger RNA were significantly lower in demented compared to nondemented HIV‐infected parients. Demented patients als had lower IL‐1β levels than did nondemented patients. No significant differences were detected in the amounts of leukemia inhibitory factor, IL‐6, transforming growth factor β1 and β2 monokine induced bygamma interferon‐2 (MIC‐2), or interferon‐Y Messenger RNSs IL‐10 and IL‐2 messenger RNAs wre undetectable in all brains examined. Cytokine messenger RNA levels in nondemented HIV‐positivew patients were similar to those in HIV‐negative control subjects. HIV transcripts were more abundant in subcortical white matter than in the basal ganglia, cortex, or deep white matter. Our findings suggest a possible role for tumor necrosis factor‐α in the development of neurological dysfunction. Increased levels of tumor necrosis factor‐α in the development of neurological dysfunction. Increased levels of tumor necrosis factor‐α messenger RNA were not associated with increased levels of IL1β messenger RNA, suggesting differential regulation of these monokines in acquired immunodeficiency syndrome dementia. Levels of IL‐4 messenger RNA were decreased in dementia and the loss of this and other macrophage downregulatory factors in demented patients may contribute to the increased expression of tumor necrosis factor‐α.
ASJC Scopus subject areas
- Clinical Neurology