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Monokine products as predictors of AIDS dementia
L Pulliam1, J A Clarke, M S McGrath
1Department of Laboratory Medicine, Veterans Affairs Medical Center, San Francisco, CA 94121, USA.
Objective:
To determine whether or not soluble factors produced by peripheral blood mononuclear cells (PBMC) can predict AIDS dementia.
Design And Methods:
PBMC were isolated from individuals with and without AIDS dementia complex (ADC) to determine if the levels of cytokines tumour necrosis factor (TNF)-alpha and interleukin (IL)-6, or the production of a neurotoxic substance, were significantly different. PBMC were studied after determining that the numbers of monocyte-derived macrophages isolated by adherence were highly variable from patients with ADC compared with individuals without ADC. We prospectively studied 16 AIDS dementia patients, 13 healthy HIV-seropositive individuals, and eight sero-negative controls. Supernatants from PBMC were assayed for TNF-alpha, IL-6 and alone for neurotoxicity on human neural cells in vitro.
Results:
We observed a trend towards worse cognitive and motor performance in patients suffering from ADC but who had no opportunistic infections ('pure dementia'; n = 8). Levels of PBMC IL-6 were significantly higher in 'pure dementia' patients. There was a trend towards lower levels of PBMC TNF-alpha in the group of patients who had both dementia and opportunistic infections compared with "pure dementia' patients. Supernatant from PBMC of ADC patients was significantly more neurotoxic than that from healthy HIV-seropositive individuals.
Conclusions:
Macrophage isolation from PBMC of patients with ADC was altered. Soluble factors produced from PBMC were significantly more neurotoxic than soluble factors from PBMC of healthy HIV-seropositive individuals. PBMC production of TNF-alpha and IL-6 was not a significant predictor of ADC.
Insights
Soluble factors from peripheral blood mononuclear cells (PBMC) of AIDS dementia complex (ADC) patients show increased neurotoxicity. While IL-6 levels were higher in some ADC patients, PBMC cytokine production did not significantly predict ADC.
Area of Science:
- Neuroscience
- Immunology
- Infectious Diseases
Background:
- AIDS dementia complex (ADC) is a debilitating neurological complication of HIV infection.
- Peripheral blood mononuclear cells (PBMC) and their soluble factors are implicated in HIV pathogenesis.
- Understanding the role of PBMC-derived factors in ADC is crucial for developing diagnostic and therapeutic strategies.
Purpose of the Study:
- To investigate whether soluble factors produced by peripheral blood mononuclear cells (PBMC) can predict AIDS dementia.
- To compare cytokine levels (TNF-alpha and IL-6) and neurotoxic substance production in PBMC from individuals with and without ADC.
Main Methods:
- Prospective study of 16 AIDS dementia patients, 13 healthy HIV-seropositive individuals, and 8 sero-negative controls.
- PBMC were isolated and cultured to assess supernatant neurotoxicity on human neural cells in vitro.
- Supernatants were assayed for levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6).
Main Results:
- A trend towards worse cognitive and motor performance was observed in patients with 'pure dementia' (ADC without opportunistic infections).
- PBMC IL-6 levels were significantly higher in 'pure dementia' patients.
- Supernatants from PBMC of ADC patients exhibited significantly greater neurotoxicity compared to healthy HIV-seropositive individuals.
Conclusions:
- Soluble factors derived from PBMC of ADC patients are significantly more neurotoxic than those from healthy HIV-seropositive individuals.
- While altered, PBMC production of TNF-alpha and IL-6 was not found to be a significant predictor of ADC.
- Macrophage isolation from PBMC of ADC patients was observed to be altered.