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.
Allan
Stuart M
SM
School of Biological Sciences, 1.124 Stopford Building, University of Manchester, Oxford Road, Manchester, M13 9PT, United Kingdom. stuart.allen@man.ac.uk
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D004660:Encephalitis / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009498:Neurotoxins / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D016207:Cytokines; D018690:Excitatory Amino Acid Agonists; D007375:Interleukin-1; D015850:Interleukin-6; D009498:Neurotoxins; D014409:Tumor Necrosis Factor-alpha; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid