The regulation of quinolinic acid in human immunodeficiency virus-infected monocytes.

Abstract

Quinolinic acid (Quin) is thought to underlie cognitive and motor dysfunctions for a variety of neurological disorders. Specifically, in human immunodeficiency virus (HIV)-associated dementia, Quin levels correlate with the degree of neurological dysfunction observed in affected individuals. Since recent data from our laboratories suggest that both HIV-1 infection and activation of brain macrophages are required for the development of neurotoxicity we examined Quin production during virus infection and immune activation. HIV-1 infection of monocytes induced low levels of Quin while lipopolysaccharide (LPS) or interferon-gamma (IFN-gamma) activation of the virus-infected cells elicited 10-fold higher levels. The combined effects of LPS and IFN-gamma for Quin production in HIV-infected monocytes was identical to each factor added alone. Little or no Quin was detected in unstimulated uninfected monocytes. LPS or IFN-gamma activation of uninfected monocytes produced substantially higher levels of Quin than found in similarly stimulated HIV-1-infected monocytes. These results were at variance to the production of tumor necrosis factor-alpha (TNF-alpha). Here, a 2-to 5-fold increase in TNF-alpha levels were observed in culture fluids of LPS-activated HIV-infected cells when compared to similarly stimulated uninfected monocytes. The effect of LPS-induced Quin production by HIV-infected monocytes was not altered by primary human astrocytes. These data suggest that Quin levels seen in HIV dementia are a reflection of macrophage/ microglial activation seen during advanced clinical disease. These findings could help explain, in part, why few HIV-1-infected brain macrophages can give rise to significant neurological impairments.

• Authors: H S Nottet, E M Flanagan, C R Flanagan, H A Gelbard, H E Gendelman, J F Reinhard Jr
• Journal: Journal of neurovirology (J Neurovirol) Vol. 2 Issue 2 Pg. 111-7 (Apr 1996) ISSN: 1355-0284 [Print] United States
• PMID: 8799202 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Quinolinic Acid

Topics

• AIDS Dementia Complex (metabolism, virology)
• Astrocytes (metabolism, virology)
• Brain (cytology, virology)
• HIV-1 (physiology)
• Humans
• Macrophages (metabolism, virology)
• Monocytes (metabolism, virology)
• Quinolinic Acid (metabolism)
• Time Factors