Department of Anesthesiology and Intensive Care Medicine, Aarhus University Hospital, Denmark.
APMIS. 2011 Feb;119(2):143-54. doi: 10.1111/j.1600-0463.2010.02704.x. Epub 2010 Dec 10.
Sepsis-induced lymphocyte apoptosis plays an important role in the development of immune suppression in septic patients. Erythropoietin (EPO) is a multifunctional cytokine with antiapoptotic properties. We hypothesized that EPO could mitigate mononuclear cell (MNC) apoptosis and modify the dynamic changes of MNCs during endotoxemia. Twenty-six pigs were randomized into three groups: (i) lipopolysaccharides (LPS), (ii) EPO (epoetin-α, 5000 IU/kg) administered 60 min prior to LPS, and (iii) sham. At 120 min of endotoxemia, the animals were fluid resuscitated and the LPS infusion was reduced. MNCs were isolated at 0, 60, 240, and 540 min of endotoxemia, and apoptosis was assessed by flow cytometry. Apoptosis in splenic biopsies was quantified by immunohistochemistry. Endotoxemia increased the number of apoptotic MNCs in the blood (p ≤ 0.01) and the spleen (p = 0.03), and EPO did not modify this increase. The number of T-helper and cytotoxic T cells declined during endotoxemia. The dynamic changes of the MNC subsets were not modified by treatment with EPO. In conclusion, EPO did not modify the LPS-induced changes of MNC subsets or mitigate the levels of apoptosis of MNCs in the blood or in the spleen. This study does not support that EPO confers protection against lymphocyte apoptosis.
脓毒症诱导的淋巴细胞凋亡在脓毒症患者免疫抑制的发展中起着重要作用。促红细胞生成素（EPO）是一种具有抗凋亡特性的多功能细胞因子。我们假设 EPO 可以减轻单核细胞（MNC）凋亡，并改变内毒素血症期间 MNC 的动态变化。26 头猪随机分为三组：（i）脂多糖（LPS），（ii）EPO（促红细胞生成素-α，5000IU/kg）在 LPS 前 60 分钟给药，和（iii）假手术。在内毒素血症 120 分钟时，对动物进行液体复苏并减少 LPS 输注。在 LPS 内毒素血症的 0、60、240 和 540 分钟时分离 MNC，并通过流式细胞术评估凋亡。通过免疫组织化学定量脾活检中的凋亡。内毒素血症增加了血液（p≤0.01）和脾脏（p=0.03）中凋亡的 MNC 数量，而 EPO 并没有改变这种增加。辅助性 T 细胞和细胞毒性 T 细胞的数量在内毒素血症期间下降。EPO 治疗并未改变 MNC 亚群的动态变化或减轻血液或脾脏中 MNC 凋亡的水平。这项研究不支持 EPO 对内毒素诱导的淋巴细胞凋亡提供保护。
