title: Enhanced expression of proinflammatory cytokines in the central nervous system is associated with neuroinvasion by simian immunodeficiency virus and the development of encephalitis.
abstract: Inflammatory cytokines are believed to play an important role in the pathogenesis of human immunodeficiency virus type 1-associated encephalitis. To examine this in the simian immunodeficiency virus (SIV)-infected macaque model of neuroAIDS, inflammatory cytokine gene expression was evaluated in the brains of macaques infected with pathogenic SIV(mac251) by reverse transcriptase PCR. Interleukin-1 beta was readily detected in the brains of all animals evaluated, regardless of infection status or duration of infection. Tumor necrosis factor alpha (TNF-alpha) and gamma interferon (IFN-gamma) transcripts were undetectable in the brains of uninfected control animals but were upregulated at 7 and 14 days postinoculation. At the terminal stage of infection, TNF-alpha and IFN-gamma transcripts were coexpressed in the brains of four of five animals with SIV encephalitis (SIVE). Within an encephalitic brain, TNF-alpha and IFN-gamma transcripts were detected in six of seven regions with histologic evidence of SIVE, suggesting a direct relationship between neuropathology and altered cytokine gene expression. With combined fluorescent in situ hybridization and immunofluorescence, TNF-alpha-expressing cells were frequently identified as CD68-positive macrophages within perivascular lesions. These observations provide evidence that cytokines produced by activated inflammatory macrophages are an important element in the pathogenesis of SIVE.
authors: New England Regional Primate Research Center, Southborough, Massachusetts 01772-9102, USA.
authors: Marlene S
authors: MS
authors: Orandle
authors: Andrew G
authors: AG
authors: MacLean
authors: Vito G
authors: VG
authors: Sasseville
authors: Xavier
authors: X
authors: Alvarez
authors: Andrew A
authors: AA
authors: Lackner
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology / Q000473:pathology; D002490:Central Nervous System / Q000276:immunology* / Q000473:pathology; D018792:Encephalitis, Viral / Q000276:immunology* / Q000473:pathology; D015870:Gene Expression; D007371:Interferon-gamma / Q000235:genetics*; D007375:Interleukin-1 / Q000235:genetics*; D008253:Macaca mulatta; D012189:Retrospective Studies; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000472:pathogenicity; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma