Interleukin-1 in the brain: mechanisms of action in acute neurodegeneration.
Interleukin-1 (IL-1) exerts a number of diverse actions in the brain, and it is currently well accepted that it contributes to experimentally induced neurodegeneration. Much of this is based on studies using the IL-1 receptor antagonist, which inhibits cell death caused by ischemia, brain injury, or excitotoxins. Our aim is to determine how and where in the brain IL-1 acts to produce these effects. Most of the neurodegenerative effects of IL-1 are thought to be through IL-1 beta. However, we have data implicating IL-1 alpha in excitotoxic cell death. Furthermore mice lacking both IL-1 alpha and IL-1 beta show dramatically reduced ischemic cell death, whereas deletion of IL-1 alpha or IL-1 beta alone fails to modify damage. It has also been demonstrated that IL-1 exacerbates ischemic injury in mice in the absence of the type I IL-1 receptor, suggesting the existence of novel IL-1 receptors in the brain. IL-1 also dramatically exacerbates neuronal loss in response to intrastriatal administration of the excitotoxin AMPA in the rat brain, an effect accompanied by marked increases in cytokine expression in the frontoparietal cortex, which precedes subsequent cell death in this region. Intrastriatal AMPA also results in limbic seizures that are exacerbated by IL-1, and we hypothesize, therefore, that IL-1 exacerbates cell death through increased seizure activity. Therefore, IL-1 appears to induce acute neurodegeneration through a number of mechanisms.
Patel
H C
HC
School of Biological Sciences, 1.124 Stopford Building, University of Manchester, Manchester, M13 9PT, UK.
Boutin
H
H
Allan
S M
SM
D000208:Acute Disease; D000818:Animals; D001921:Brain / Q000276:immunology*; D001930:Brain Injuries / Q000276:immunology / Q000503:physiopathology; D002545:Brain Ischemia / Q000276:immunology / Q000503:physiopathology; D004195:Disease Models, Animal; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D051379:Mice; D009410:Nerve Degeneration / Q000276:immunology* / Q000503:physiopathology; D011994:Recombinant Proteins / Q000276:immunology; D012640:Seizures / Q000276:immunology
D007375:Interleukin-1; D011994:Recombinant Proteins