Role of the pro-inflammatory cytokines TNF-alpha and IL-1beta in HIV-associated dementia.
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.
Brabers
N A C H
NA
Department of Virology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands.
Nottet
H S L M
HS
D015526:AIDS Dementia Complex / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D001921:Brain / Q000276:immunology; D016923:Cell Death / Q000276:immunology; D015870:Gene Expression / Q000235:genetics; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D017628:Microglia / Q000276:immunology; D009474:Neurons / Q000276:immunology; D018696:Neuroprotective Agents / Q000276:immunology; D009498:Neurotoxins / Q000276:immunology; D016194:Receptors, N-Methyl-D-Aspartate / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D007375:Interleukin-1; D018696:Neuroprotective Agents; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D014409:Tumor Necrosis Factor-alpha