Rothwell N J, Relton J K
Department of Physiological Sciences, University of Manchester, England.
Cerebrovasc Brain Metab Rev. 1993 Fall;5(3):178-98.
The cytokine interleukin-1 (IL-1) is synthesised within the brain and acts as a mediator of host defence responses to disease and injury. Several of these central actions of IL-1 are inhibited by an endogenous calcium and phospholipid binding protein, lipocortin-1. Synthesis of IL-1 and lipocortin-1 in the brain is markedly increased by neuronal damage, and inhibition of the actions of endogenous IL-1 by central injection of IL-1 receptor antagonist in the rat significantly inhibits ischaemic and excitotoxic brain damage. Lipocortin-1 appears to act as an endogenous neuroprotective agent that markedly attenuates ischaemic and excitotoxic damage. In contrast, inhibition of the actions of lipocortin-1 by injection of neutralising antiserum exacerbates both forms of neurodegeneration. The mechanisms underlying these effects of IL-1 and lipocortin-1 are largely unknown, but are probably independent of changes in body temperature. Actions of these molecules on corticotrophin releasing factor, arachidonic acid, excitatory amino acids, and nitric oxide, and the possible involvement of these factors in brain damage are discussed.
细胞因子白细胞介素-1（IL-1）在脑内合成，是机体对疾病和损伤的宿主防御反应的介质。IL-1的这些中枢作用中有几种会被一种内源性钙和磷脂结合蛋白——脂皮质蛋白-1所抑制。神经元损伤会显著增加脑内IL-1和脂皮质蛋白-1的合成，而在大鼠脑内中央注射IL-1受体拮抗剂抑制内源性IL-1的作用，可显著抑制缺血性和兴奋性毒性脑损伤。脂皮质蛋白-1似乎作为一种内源性神经保护剂，可显著减轻缺血性和兴奋性毒性损伤。相反，注射中和抗血清抑制脂皮质蛋白-1的作用会加重这两种形式的神经退行性变。IL-1和脂皮质蛋白-1这些作用的潜在机制很大程度上尚不清楚，但可能与体温变化无关。讨论了这些分子对促肾上腺皮质激素释放因子、花生四烯酸、兴奋性氨基酸和一氧化氮的作用，以及这些因子可能参与脑损伤的情况。
