Toxicity of TNF alpha and platelet activating factor for human NT2N neurons: a tissue culture model for human immunodeficiency virus dementia.

Abstract

A significant proportion of HIV-1 infected individuals develop a symptom complex consisting of dementia and motor deficits termed HIV Dementia (HIVD) or the AIDS Dementia complex (ADC). The pathophysiology of this neurologic complication is unclear, but neuronal injury and death may occur as a direct result of the release of cytokines from HIV-1 infected microglial cells (Everall et al, 1991). To evaluate the utility of a human neuronal cell line, NT2N, for studies of HIV-related neuronal cytotoxicity, we studied cellular viability after exposure to HIV-1 gp120, tumor necrosis factor alpha (TFN alpha), platelet activating factor (PAF), interleukin 1 beta (IL-1 beta), and interferon gamma (IFN gamma), all of which have been implicated in previous publications as having a role in HIVD (Brenneman et al, 1988; Dreyer et al, 1990; Merrill et al, 1992; Gelbard et al, 1993). Neither gp 120 nor the cytokines IL-1 beta and IFN gamma resulted in significant NT2N cell death. However, TNF alpha and PAF were highly neurotoxic in this assay. Pentoxifylline, which inhibits the effects of TNF alpha, had a significant protective effect. This system provides an excellent substrate for the evaluation of neurotoxicity and for the development of pharmacologic agents that may be useful in HIV dementia.