Cytokines in neurodegeneration and repair

Publisher Website
Google Scholar
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 α, 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‐1β 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 (μM 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.