Interleukin-10 reduces morbidity and mortality in murine multiple organ dysfunction syndrome (MODS)

Interleukin-10 reduces morbidity and mortality in murine multiple organ dysfunction syndrome (MODS)
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DOI:
10.1006/jsre.1998.5372
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发表时间:
1998-07-01
影响因子:
2.2
通讯作者:
Cone, JB
Cone, JB
中科院分区:
医学3区
文献类型:
--
作者:
Ferrer, TJ;Webb, JW;Cone, JB

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假说. IL-10可降低小鼠MODS的发病率和死亡率。腹膜内(ip)酵母多糖引起导致MODS的三阶段炎症过程。I期是对无菌性腹膜炎的急性全身炎症反应。第二阶段是恢复阶段。III期的特征是疾病复发、进行性器官功能障碍和促炎细胞因子升高。将雄性ICR小鼠随机(在实验第0天,时间= 0小时)分成四个初始组(A-D):对照组A不接受酵母聚糖且不接受IL-10,组B接受酵母聚糖(1 mg/g小鼠BW,t = 0)且不接受IL-10。C组在t = 2 h时不给予酵母多糖和IL-10。D组在t = 2 h时给予酵母多糖和IL-10。在实验第4天,将B-D组中的小鼠随机分为另外6个处理组(B1和B2、C1和C2、D1和D2)。B1组不做任何处理。B2组在出现复发性疾病的临床体征时接受IL-10(III期,酵母聚糖治疗后12-18天)。在终末前(颤抖、颤抖或麻痹的临床体征)或实验第28天(存活)处死小鼠。血浆总胆红素和肌酐水平仅仅是器官功能的指标。在生理潮气量范围内原位测量终末肺顺应性。进入III期的小鼠持续进展为MODS,其特征为胆红素升高和肺出血,如果不治疗,则是致命的。用IL-10处理的小鼠(B2组)进入III期时死亡率较低(28.6%比100%,P < 0.02),生存期延长(25 vs 18 d,P < 0.05),改善肺顺应性(斜率β(1)= 0.082 ml/mm Hg vs 0.059 ml/mm Hg,P < 0.001)。即使在存在疾病的临床体征之后给予IL-10也可改善存活率。(C)北京:科学出版社.
Hypothesis. IL-10 mill reduce morbidity and mortality in murine MODS.Introduction. Intraperitoneal (ip) zymosan causes a triphasic inflammatory process leading to MODS. Phase I is an acute systemic inflammatory response to sterile peritonitis. Phase II is the recovery phase. Phase III is characterized by recurrent illness, progressive organ dysfunction, and elevated proinflammatory cytokines.Methods. Male ICR mice were randomized (on Experiment Day 0, time = 0 h) into four initial groups (A-D): Control Group A received no zymosan and no IL-10, Group B received zymosan (1 mg/g mouse BW, t = 0) and no IL-10. Group C received no zymosan and IL-IO at t = 2 h. Group D received zymosan and IL-IO at t = 2 h. On Experiment Day 4, mice in Groups B-D were randomized into six further treatment groups (B1 and B2, C1 and C2, D1 and D2). Group B1 received no treatment. Group B2 received IL-10 when clinical signs of recurrent illness developed (Phase III, 12-18 days after zymosan treatment). Mice were sacrificed when they were preterminal (clinical signs of shaking, shivering, or paralysis) or on Experiment Day 28 (survivors). Plasma total bilirubin and creatinine levels mere measures of organ function. Terminal pulmonary compliance was measured in situ through a physiologic range of tidal volumes.Results. Mice entering Phase III consistently progressed to MODS characterized by elevated bilirubin and hemorrhagic lungs which, if left untreated, was lethal. Mice treated with IL-10 (Group B2) when they entered Phase III had lower mortality (28.6% vs 100%, P < 0.02), longer survival (25 vs 18 days, P < 0.05), and improved lung pulmonary compliance (slope beta(1) = 0.082 ml/mm Hg vs 0.059 ml/mm Hg, P < 0.001) compared to untreated (Group B1) mice in Phase III.Conclusions. IL-IO improves survival even when given after clinical signs of illness are present. (C) 1998 Academic Press.