Brew BJ, Pemberton L, Heyes M, Evans L; International Conference on AIDS.
Int Conf AIDS. 1993 Jun 6-11; 9: 61 (abstract no. WS-B18-2).
Centre for Immunology, St Vincent's Hospital, Sydney, Australia.
OBJECTIVES: We have previously reported that Quinolinic acid (QUIN), a neurotoxin acting through the N Methyl D Aspartate receptor, is markedly elevated in the cerebrospinal fluid (CSF) of patients with AIDS dementia complex (ADC) and is produced by HIV-1 infected and interferon stimulated macrophages. We sought to address the following hypotheses: i) that HIV infected macrophages produce QUIN not through HIV infection per se but through the concomitant production of cytokines, ii) that CSF isolates of HIV-1 from demented patents produce more QUIN than from non-demented patients. METHODS: Human macrophages were isolated from peripheral blood mononuclear cells by glass adherence and grown in monomed and then AIMV. The cells were then infected by HIV-1 SF2 and once a productive infection had been obtained the supernatants were filtered and centrifuged. The resulting pellet was resuspended in AIMV and was used to inoculate another set of macrophages. Production of QUIN was assessed at 0, 24, 36, 48 and 60 hours. In the second experiment, the production of QUIN by macrophages infected with CSF isolates taken from patients with ADC stage 0 and ADC stage 3 as undertaken. These isolates had been previously characterised as being macrophage tropic or non macrophage tropic according to amount of p24 that was detected in the supernatants over a 30 day period. Equal numbers of macrophages were used for this experiment and cell death was quantified at each time point for QUIN analysis by the MTT assay. To substantiate that QUIN was produced by the kynurenine pathway, [13C6]-tryptophan was added to the media for each of the latter experiments. RESULTS: Macrophages infected with "pelleted" HIV-1 did not produce QUIN. Macrophages infected with demented isolates variably produced more QUIN than those infected with non-demented isolates. The variability seemed at least in part related to whether macrophage tropic or non macrophage tropic isolates were used. CONCLUSIONS: Macrophage production of QUIN is not dependent on HIV-1 infection of the macrophage per se but is more likely the result of the concomitant production of various cytokines. The finding of QUIN production by macrophages infected with isolates from demented and non-demented patients further supports a role for QUIN in ADC and its probable production by cytokines strengthens the cytokine model for the pathogenesis of ADC.
Publication Types:
Keywords:
- AIDS Dementia Complex
- AIDS Vaccines
- Acquired Immunodeficiency Syndrome
- Anti-HIV Agents
- Cytokines
- HIV
- HIV Envelope Protein gp120
- HIV Infections
- HIV Seronegativity
- HIV Seropositivity
- HIV-1
- Humans
- Kynurenine
- Macrophages
- Neurotoxins
- Quinolinic Acid
- Tryptophan
- immunology
Other ID:
UI: 102205630
From Meeting Abstracts