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Eur J Clin Invest. 2006 Jul;36(7):447-58.

Role of the pro-inflammatory cytokines TNF-alpha and IL-1beta in HIV-associated dementia.

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Department of Virology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands.


Human immunodeficiency virus-1 (HIV-1)-infected and immune-activated macrophages and microglia secrete neurotoxins. Two of these neurotoxins are the pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), which are thought to play a major role in inducing neuronal death. Both TNF-alpha and IL-1beta increase the permeability of the blood-brain barrier, through which subsequently HIV-infected monocytes can enter the brain. They both induce over-stimulation of the NMDA-receptor via several pathways, resulting in a lethal neuronal increase in Ca(2+) levels. Additionally, TNF-alpha co-operates with several other proinflammatory mediators to enhance their toxic effects. Although most research has focused on the neurotoxic effects of TNF-alpha and IL-1beta in HAD, there is also evidence that these cytokines can be neuroprotective. In this paper the effect of TNF-alpha and IL-1beta on neuronal life and death in HAD is discussed.

[Indexed for MEDLINE]

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