title: Cytokines in neurodegeneration and repair.
abstract: Cytokines have diverse actions in the brain, some of which may facilitate either neurodegeneration or neuroprotection. The expression of cytokines, particularly interleukins-1 and -6 (IL-1, IL-6) and tumor necrosis factor alpha, is rapidly and markedly induced in response to experimentally induced or clinical neurodegeneration. We have demonstrated that central administration of the IL-1 receptor antagonist (IL-1ra) markedly inhibits neurodegeneration induced by focal cerebral ischaemia, local infusion of glutamate receptor agonists or traumatic brain injury in the rat. In contrast, IL-1ra offers no protection against degeneration of primary cortical neurones in culture caused by exposure to agonists of ionotrophic or metabotrophic receptors. In vivo, administration of IL-1 beta exacerbates ischaemic brain damage, whereas in cell culture, exogenous IL-1 is neuroprotective at concentrations in the nM range, an effect which appears to be mediated by release of endogenous nerve growth factor. Higher concentrations of IL-1 (microM range) are neurotoxic to neurones in culture and may mimic the involvement of IL-1 in neurodegeneration in vivo. Thus, excessive production of cytokines such as IL-1 appears to mediate experimentally induced neurodegeneration in vivo, while neuroprotective effects of low concentrations of the cytokine suggest a dual role for IL-1 in neuronal survival.
authors.affiliation: School of Biological Sciences, University of Manchester, U.K.
authors.forename: N J
authors.initials: NJ
authors.lastname: Rothwell
authors.forename: P J
authors.initials: PJ
authors.lastname: Strijbos
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D007378:Interleukins / Q000502:physiology; D009410:Nerve Degeneration / Q000502:physiology*; D009416:Nerve Regeneration / Q000502:physiology*; D051381:Rats
chemical_list: D016207:Cytokines; D007378:Interleukins