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

Interleukin (IL)-1beta mediates diverse forms of neurodegeneration and exacerbates cell death induced by striatal injection of the excitotoxin alpha-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-1beta. Injection of IL-1alpha and AMPA in the striatum had effects identical to those of IL-1beta, whereas coinjection of IL-6 or tumor necrosis factor (TNF)-alpha with AMPA failed to induce significant cortical cell death. In contrast to IL-1alpha, IL-1beta, and IL-6, TNFalpha 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, TNFalpha shows neuroprotective effects against acute excitotoxic injury.