Chao CC, Hu S, Ehrlich L, Peterson PK.
Interleukin-1 and tumor necrosis factor-alpha synergistically mediate neurotoxicity: involvement of nitric oxide and of N-methyl-D-aspartate receptors, Brain Behav Immun 9(4) :355-65, 1995.
Abstract
The cytokines interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha, produced by glial cells within the brain, appear to contribute to the
neuropathogenesis of several inflammatory neurodegenerative diseases; however, little is known about the mechanism underlying
cytokine-induced neurotoxicity. Using human fetal brain cell cultures composed of neurons and glial cells, we investigated the injurious
effects of IL-1beta and TNF-alpha, cytokines which are known to induce nitric oxide (NO) production by astrocytes. Although neither
cytokine alone was toxic, IL-1beta and TNF-alpha in combination caused marked neuronal injury. Brain cell cultures treated with IL-1beta
plus TNF-alpha generated substantial amounts of NO. Blockade of NO production with a NO synthase inhibitor was accompanied by a
marked reduction (about 45%) of neuronal injury.
Important Points:
-Model: human fetal neuron-glial cultures
-IL-1B or TNF-a alone are not toxic, but in combination cause neural damage, which could be partially attenuated by blocking NO synthesis
- NO production by astrocytes may therefore play a role in cytokine-induced
neurotoxicity.
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