Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan.
Cytokine. 2010 Feb;49(2):155-62. doi: 10.1016/j.cyto.2009.11.002. Epub 2009 Dec 8.
Endotoxin shock can induce the production of several inflammatory mediators such as TNF-alpha, IL-6, and IL-1beta, leading to multiple organ dysfunction and death. Erythropoietin (EPO) has been found to interact with its receptor (EPO-R), expressed in a wide variety of non-hematopoietic tissues, to induce a range of pleiotropic cytoprotective actions. We investigated the effects of low doses of EPO (300U/kg, intravenous administration) on the physiopathology and cytokine levels in endotoxin shock in conscious rats. Endotoxin shock was induced by intravenous injection of Escherichia coli lipopolysaccharide (20mg/kg) in conscious rats. Mean arterial pressure (MAP) and heart rate (HR) were continuously monitored for 48h after LPS administration. Levels of biochemical and cytokine parameters, including glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), blood urea nitrogen (BUN), creatinine (Cre), lactic dehydrogenase (LDH), and creatine phosphokinase (CPK) were measured at 0, 1, 3, 6, 9, 12, 18, 24, and 48h after sepsis. Serum TNF-alpha, IL-6, and IL-1beta level was measured at 1h after sepsis. Endotoxin shock significantly increased blood GOT, GPT, BUN, Cre, LDH, CPK, TNF-alpha, IL-6, IL-1beta levels, and HR, while it decreased MAP. EPO further increased the markers of organ injury (GOT, GPT, BUN, Cre, LDH, and CPK), inflammatory biomarkers (TNF-alpha, IL-6, and IL-1beta) and did not affect MAP and HR after LPS. EPO disserved endotoxin shock-induced liver, kidney, lung, and small intestine damage in conscious rats. In conclusion, pre-treatment with low doses of EPO increased the release of TNF-alpha, IL-6, and IL-1beta, along with aggravating endotoxin shock-induced markers of organ injury in conscious rats.
内毒素休克可诱导 TNF-α、IL-6 和 IL-1β 等多种炎症介质的产生，导致多器官功能障碍和死亡。促红细胞生成素（EPO）已被发现与其受体（EPO-R）相互作用，EPO-R 在广泛的非造血组织中表达，可诱导多种多效性细胞保护作用。我们研究了小剂量 EPO（300U/kg，静脉注射）对内毒素休克在清醒大鼠中的病理生理学和细胞因子水平的影响。在清醒大鼠中，通过静脉注射大肠杆菌脂多糖（20mg/kg）诱导内毒素休克。在 LPS 给药后 48 小时内连续监测平均动脉压（MAP）和心率（HR）。在败血症后 0、1、3、6、9、12、18、24 和 48 小时测量生化和细胞因子参数（包括谷草转氨酶（GOT）、谷丙转氨酶（GPT）、血尿素氮（BUN）、肌酐（Cre）、乳酸脱氢酶（LDH）和肌酸磷酸激酶（CPK））的水平。在败血症后 1 小时测量血清 TNF-α、IL-6 和 IL-1β 水平。内毒素休克显著增加血液 GOT、GPT、BUN、Cre、LDH、CPK、TNF-α、IL-6 和 IL-1β 水平和 HR，同时降低 MAP。EPO 进一步增加了器官损伤标志物（GOT、GPT、BUN、Cre、LDH 和 CPK）、炎症生物标志物（TNF-α、IL-6 和 IL-1β），并且对 LPS 后的 MAP 和 HR 没有影响。EPO 对内毒素休克诱导的清醒大鼠肝、肾、肺和小肠损伤没有保护作用。总之，小剂量 EPO 预处理增加了 TNF-α、IL-6 和 IL-1β 的释放，并加重了清醒大鼠内毒素休克诱导的器官损伤标志物。
