Coleman Thomas, Brines Michael
The Kenneth S Warren Institute, Kitchawan, New York, USA.
Crit Care. 2004 Oct;8(5):337-41. doi: 10.1186/cc2897. Epub 2004 Jun 16.
Erythropoiesis usually fails during severe illness because of a blunting of the kidney-erythropoietin (EPO)-bone marrow axis. In this setting, clinical studies have shown that recombinant human erythropoietin (rhEPO), administered in pharmacological amounts, significantly reduces the need for blood transfusions. In addition to the kidney, however, EPO is also produced locally by other tissues in a paracrine-autocrine manner. Here, similar to its role in the bone marrow, EPO rescues cells from apoptosis. Additionally, EPO reduces inflammatory responses, restores vascular autoregulation, and promotes healing. The results of many studies (including a phase II clinical trial in ischemic stroke) demonstrate that rhEPO protects the brain, spinal cord, retina, heart, and kidney from ischemic and other types of injury. Although rhEPO is efficacious in the treatment of EPO-deficient anemia during illness, inadequate effort has been devoted to determining whether direct tissue protection might also result from its administration. Here, we speculate on the potential utility of EPO as a protective cytokine in the context of acute critical illness and suggest key parameters required for a proof-of-concept clinical study.
在严重疾病期间，红细胞生成通常会失败，因为肾 - 促红细胞生成素（EPO） - 骨髓轴受到抑制。在这种情况下，临床研究表明，给予药理剂量的重组人促红细胞生成素（rhEPO）可显著减少输血需求。然而，除了肾脏外，EPO还由其他组织以旁分泌 - 自分泌方式在局部产生。在这里，与它在骨髓中的作用类似，EPO可使细胞免于凋亡。此外，EPO可减轻炎症反应，恢复血管自动调节，并促进愈合。许多研究（包括一项缺血性中风的II期临床试验）结果表明，rhEPO可保护脑、脊髓、视网膜、心脏和肾脏免受缺血及其他类型的损伤。尽管rhEPO在治疗疾病期间的EPO缺乏性贫血方面有效，但在确定其给药是否也可能产生直接的组织保护作用方面，所做的努力还不够。在此，我们推测EPO作为一种保护性细胞因子在急性危重病中的潜在效用，并提出概念验证临床研究所需的关键参数。
