Dementia in AIDS Patients: A TNF Producing Factor?
Abstract & Commentary
Synopsis: A recent study showed that monocytes from demented AIDS patients had a greater chance of producing TNF but no more than those HIV patients without dementia.
Source: Pulliam L, et al. Unique monocyte subset in patients with AIDS dementia. Lancet 1997;349:692-695.
Up to 30% of patients with hiv infection will develop debilitating dementia. There are several studies linking certain serum or CSF markers such as neopterin and b2 microglobulin that are elevated in patients with neurological involvement. Pulliam et al from UC San Francisco and a neurobioscience company called Neurex were more interested in detecting soluble factors produced by peripheral blood mononuclear cells that could predict dementia. Therefore, they looked at 12 HIV-positive patients with dementia and 11 without dementia for such soluble factors.
Because the monocyte is the cell in the brain that is primarily affected (unlike the CD4+ lymphocyte in the periphery), these workers separated subsets of monocytes. Peripheral monocytes probably cross the blood-brain barrier and develop into brain macrophages. Certain substances are released from HIV-activated peripheral macrophages such as tissue necrosis factor a platelet activating factor, arachidonic acid metabolites, and quinolinic acid. In brains of HIV-positive patients, only TNF and quinolinic acid are increased.
The results of this study showed that monocytes from demented AIDS patients had a greater chance of producing TNF but no more than those HIV patients without dementia. A cell-surface molecule known as CD16 that represents a type of Fc receptor was also increased in AIDS patients and increased to a greater degree in AIDS-demented patients.
One more interesting experiment was performed. It was found that a monocyte subset marker, CD69, was elevated in patients with AIDS dementia. The supernatants from CD69-positive monocytes of the HIV-demented patients were incubated with brain aggregated cells for 72 hours and programmed cell death-apoptosis was measured. Compared to controls, there was a huge increase in apoptosis as measured by DNA fragmentation but not in necrotic cell death.
COMMENT BY JOSEPH F. JOHN, MD
Though this is not a large study, it focuses on a troublesome part of the AIDS epidemic: those patients who advance to debilitating dementia. This study found that monocytes that can traffic in and out of the brain are covered by a specific receptor, CD69, that is associated with initiating programmed cell death of brain cells. It is known that CD69 can be crosslinked on the surface of cells and, as such, induced calcium influx, prosta-glandin E2, nitric oxide, and arachidonic acid metabolites.
How could information like this be used clinically? I suspect that, in time, we will use flow cytometry derived indicators to characterize the types of PBMC that are infected in individual HIV patients. From such a profilelet us say a predominance of CD69 positive PBMCsthere may be a greater risk of dementia prompting earlier therapeutic intervention with CNS active agents.
The authors of this article suggestand they may be justifiedthat a specific "objective" marker would be very helpful in studying AIDS dementia. Perhaps, in time, these unique monocyte subsets could be used for neuroimaging to detect their trafficking into CNS and for the CNS response to antiretroviral chemotherapy.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content