Pellicane J V, DeMaria E J, Abd-Elfattah A, Reines H D, Vannice J L, Carson K W
Department of Surgery, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298-0475.
Surgery. 1993 Aug;114(2):278-83; discussion 283-4.
This study was designed to determine the role of interleukin-1 (IL-1) in hemorrhagic shock death.
Pentobarbital anesthetized C3H/HeN mice (n = 59) were prepared with a femoral arterial catheter and were randomized to treatment with an IL-1 receptor antagonist (IL-1ra, 10 mg/kg, n = 29) or an equal volume of phosphate-buffered saline solution (vehicle, n = 30) by subcutaneous bolus injection at 15 minutes before hemorrhage and again at 120 minutes. Continuous posthemorrhage delivery of IL-1ra or vehicle was performed in each group (1.5 mg IL-1ra in 30 microliters/day) through a subcutaneous osmotic pump. Rapid hemorrhage of 4 ml/100 gm weight was followed by normal saline resuscitation of 12 ml/100 gm 60 minutes later.
Survival analysis by Wilcoxon rank sum analysis revealed a significantly improved 5-day survival in IL-1ra-treated mice (n = 15, 20%) as compared with vehicle-treated mice (n = 14, 6%, p < 0.001). To determine a possible mechanism of this survival advantage, the remaining mice in each treatment group were killed at 30 minutes to obtain blood and tissue samples from the heart, liver, and kidney for measurement of adenosine-5'-triphosphate (ATP). No difference in hematocrit, circulating neutrophils, or levels of glucose, lactate, or tumor necrosis factor was identified between groups to explain the improved outcome. IL-1ra prevented hemorrhage-induced ATP depletion observed in vital organs of vehicle-treated mice.
The data implicate IL-1 in shock-induced ATP depletion and suggest IL-1ra may improve hemorrhagic shock survival by preventing ATP depletion in vital organs.
本研究旨在确定白细胞介素-1（IL-1）在失血性休克死亡中的作用。
用戊巴比妥麻醉C3H/HeN小鼠（n = 59），并插入股动脉导管，在出血前15分钟和120分钟时随机分为两组，分别皮下推注白细胞介素-1受体拮抗剂（IL-1ra，10 mg/kg，n = 29）或等体积的磷酸盐缓冲盐水溶液（载体，n = 30）。每组通过皮下渗透泵持续输注IL-1ra或载体（每天30微升含1.5 mg IL-1ra）。以4 ml/100 gm体重的速度快速出血，60分钟后用12 ml/100 gm生理盐水进行复苏。
通过Wilcoxon秩和分析进行生存分析发现，与载体处理组小鼠（n = 14，6%，p < 0.001）相比，IL-1ra处理组小鼠（n = 15，20%）的5天生存率显著提高。为了确定这种生存优势的可能机制，在30分钟时处死每个治疗组的其余小鼠，以获取心脏、肝脏和肾脏的血液和组织样本，用于测量三磷酸腺苷（ATP）。两组之间在血细胞比容、循环中性粒细胞或葡萄糖、乳酸或肿瘤坏死因子水平方面未发现差异，无法解释这种改善的结果。IL-1ra可防止在载体处理组小鼠重要器官中观察到的出血诱导的ATP耗竭。
数据表明IL-1参与休克诱导的ATP耗竭，并提示IL-1ra可能通过防止重要器官中的ATP耗竭来提高失血性休克的生存率。
