Erythropoietin exerts an anti-inflammatory effect on the CNS in a model of experimental autoimmune encephalomyelitis
Erythropoietin exerts an anti-inflammatory effect on the CNS in a model of experimental autoimmune encephalomyelitis
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DOI：
10.1016/s0006-8993(02)03239-0
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发表时间：
2002-10-11
期刊：
影响因子：
2.9
通讯作者：
Ghezzi, P
中科院分区：
文献类型：
--
作者：
Agnello, D;Bigini, P;Ghezzi, P
在最近的工作中，我们报道了全身给药的促红细胞生成素（EPO）穿过血脑屏障，并在脑缺血，脑外伤的动物模型和实验性自身免疫性脑脊髓炎（EAE）的大鼠模型中具有保护作用。在这里，我们描述了全身性EPO对刘易斯大鼠主动诱导的急性EAE炎症组分的影响。以500-5000 U/kg bw的剂量腹膜内给予EPO，从髓鞘碱性蛋白（MBP）免疫后第3天开始，每天注射一次，可延迟EAE的发病，并降低高峰期（第12-13天）的临床评分。脊髓使用抗胶质细胞酸性蛋白（GFAP）和抗CD 11b抗体的免疫组织化学分析表明，EPO显着减少炎症和胶质细胞活化/增殖。EAE在脊髓中诱导显著水平的TNF和IL-6，其中IL-6在疾病发作时（第10天）最大，TNF在其峰值（第12天）。EPO延迟了TNF水平的增加，而不改变其峰值水平，并显著降低了IL-6的水平，这表明炎症和临床评分的降低可能部分是由于IL-6的减弱。另一方面，EPO在刘易斯大鼠的抗炎药诱导的关节炎模型中没有作用，表明对自身免疫性脱髓鞘疾病具有特异性。这些数据表明，促红细胞生成素可能作为一种保护性细胞因子在中枢神经系统的炎症病理。(C)2002 Elsevier Science B. V.保留所有权利。
In recent work we reported that systemically administered erythropoietin (EPO) crosses the blood-brain barrier and has protective effects in animal models of cerebral ischemia, brain trauma and in a rat model of experimental autoimmune encephalomyelitis (EAE). Here we characterize the effect of systemic EPO on the inflammatory component of actively induced, acute EAE in Lewis rats. Administration of EPO at doses of 500-5000 U/kg bw i.p., daily from day 3 after immunization with myelin basic protein (MBP), delayed the onset of EAE and decreased its clinical score at peak time (days 12-13). Immunohistochemical analysis of the spinal cord using anti-glial fibrillary acidic protein (GFAP) and anti-CD11b antibodies showed that EPO markedly diminished inflammation and glial activation/proliferation. EAE induced significant levels of TNF and IL-6 in the spinal cord, where IL-6 was maximum at the onset of the disease (day 10) and TNF at its peak (day 12). EPO delayed the increase of TNF levels, without altering their peak levels, and markedly reduced those of IL-6 suggesting that the decreased inflammation and clinical score may be in part upon attenuation of IL-6. On the other hand, EPO was without effect in a model of adjuvant-induced arthritis in Lewis rats, suggesting a specificity towards autoimmune demyelinating diseases. These data suggest that EPO might act as a protective cytokine in inflammatory pathologies of the CNS. (C) 2002 Elsevier Science B.V. All rights reserved.