Enhanced expression of proinflammatory cytokines in the central nervous system is associated with neuroinvasion by simian immunodeficiency virus and the development of encephalitis.
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.
Orandle
Marlene S
MS
New England Regional Primate Research Center, Southborough, Massachusetts 01772-9102, USA.
MacLean
Andrew G
AG
Sasseville
Vito G
VG
Alvarez
Xavier
X
Lackner
Andrew A
AA
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*
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma