Varied actions of proinflammatory cytokines on excitotoxic cell death in the rat central nervous system

Interleukin (IL)-1β mediates diverse forms of neurodegeneration and exacerbates cell death induced by striatal injection of the excitotoxin α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) in the rat brain. The objective of this study was to determine whether this effect was specific to IL-1β. Injection of IL-1α and AMPA in the striatum had effects identical to those of IL-1β, whereas coinjection of IL-6 or tumor necrosis factor (TNF)-α with AMPA failed to induce significant cortical cell death. In contrast to IL-1α, IL-1β, and IL-6, TNFα significantly reduced (by 38%) the local striatal damage. These findings suggest that the effect of IL-1 on AMPA receptor-mediated cell death in the rat striatum is not mimicked by other proinflammatory cytokines. Furthermore, TNFα shows neuroprotective effects against acute excitotoxic injury. © 2002 Wiley-Liss, Inc.