Ferrer T J, Webb J W, Wallace B H, Bridges C D, Palmer H E, Robertson R D, Cone J B
Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas, 72205, USA.
J Surg Res. 1998 Jul 1;77(2):157-64. doi: 10.1006/jsre.1998.5372.
IL-10 will 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.
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-10 at t = 2 h. Group D received zymosan and IL-10 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 were measures of organ function. Terminal pulmonary compliance was measured in situ through a physiologic range of tidal volumes.
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 beta1 = 0.082 ml/mm Hg vs 0.059 ml/mm Hg, P < 0.001) compared to untreated (Group B1) mice in Phase III.
IL-10 improves survival even when given after clinical signs of illness are present.
白细胞介素-10可降低小鼠多器官功能障碍综合征的发病率和死亡率。引言。腹腔注射酵母聚糖会引发一个导致多器官功能障碍综合征的三相炎症过程。第一阶段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。第三阶段的特征是病情复发、进行性器官功能障碍以及促炎细胞因子升高。
雄性ICR小鼠被随机分组（在实验第0天，时间=0小时）为四个初始组（A - D）：对照组A未接受酵母聚糖和白细胞介素-10。B组接受酵母聚糖（1毫克/克小鼠体重，时间=0）且未接受白细胞介素-10。C组在时间=2小时时未接受酵母聚糖但接受白细胞介素-10。D组在时间=2小时时接受酵母聚糖和白细胞介素-10。在实验第4天，B - D组的小鼠被进一步随机分为六个治疗组（B1和B2、C1和C2、D1和D2）。B1组未接受治疗。B2组在病情复发的临床体征出现时（第三阶段，酵母聚糖治疗后12 - 18天）接受白细胞介素-10。当小鼠处于濒死前状态（出现颤抖、寒战或瘫痪的临床体征）或在实验第28天（存活者）时将其处死。血浆总胆红素和肌酐水平是器官功能的指标。通过潮气量的生理范围原位测量终末肺顺应性。
进入第三阶段的小鼠持续发展为以胆红素升高和肺出血为特征的多器官功能障碍综合征，若不治疗则会致死。进入第三阶段时接受白细胞介素-10治疗的小鼠（B2组）与第三阶段未治疗的小鼠（B1组）相比，死亡率更低（28.6%对100%，P<0.02），存活时间更长（25天对18天，P<0.05），肺顺应性得到改善（斜率β1 = 0.082毫升/毫米汞柱对0.059毫升/毫米汞柱，P<0.001）。
即使在出现疾病临床体征后给予白细胞介素-10也能提高存活率。
