Interleukin-10 reduces the systemic inflammatory response in a murine model of intestinal ischemia/reperfusion

Interleukin-10 reduces the systemic inflammatory response in a murine model of intestinal ischemia/reperfusion
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DOI:
10.1016/s0039-6060(97)90020-9
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发表时间:
1997-08-01
期刊:
影响因子:
3.8
通讯作者:
Chandler, CF
Chandler, CF
中科院分区:
医学2区
文献类型:
--
作者:
Lane, JS;Todd, KE;Chandler, CF

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背景资料。众所周知,肠缺血/再灌注(I/R)可增加全身细胞因子水平,并激活远处器官中的中性粒细胞。本研究旨在探讨白细胞介素10(IL-10)对小鼠I/R模型细胞因子释放、肺中性粒细胞聚集及组织学改变的影响。将40只雌性瑞士-韦氏小鼠分成4组。组1结扎肠系膜上动脉45min,再灌注3h。第2组为单纯开腹(Sham)组。第3组为I/R组,再灌流前1小时开始,每2小时1次,每次10000单位;第4组为等量IL-10,再灌流后1小时开始。3h后处死动物,常规测定血清细胞因子水平,并进行肺组织髓过氧化物酶活性和肠道组织学检查。再灌流前后应用IL-10后,血清细胞因子(TNF-α和IL-6)、肺组织髓过氧化物酶水平和组织学评分均显著降低。IL-10可降低肠I/R模型小鼠在再灌注损伤前后局部和全身炎症的严重程度。这些观察表明,IL-10可能通过阻断细胞因子的产生和远端器官中性粒细胞的聚集而发挥作用。
Background. Intestinal ischemia/reperfusion (I/R) is known to increase systemic cytokine levels, as well as to activate neutrophils in distant organs. This study was designed to investigate the effect of interleukin-10 (IL-10) on cytokine release, pulmonary neutrophil accumulation, and histologic changes in a murine model of I/R.Methods. Forty female Swiss-Webster mice were divided into four groups. Group 1 underwent 45 minutes of superior mesenteric artery occlusion followed by 3-hour reperfusion (I/R). Group 2 underwent laparotomy alone (Sham). Group 3 underwent I/R, but was treated with IL-10, 10,000 units IP every 2 hours, starting 1 hour before reperfusion (Pretreatment), Group 4 was treated with an equal dose of IL-10, starting 1 hour after reperfusion (Posttreatment). All animals were killed at 3 hours, standard assays were performed for serum cytokine levels, and lung myeloperoxidase activity and intestinal histology were scored.Results. Serum cytokines (TNF-alpha and IL-6), lung myeloperoxidase levels, and histologic score were significantly reduced when IL-10 was administered either before or after reperfusion.Conclusions. IL-10 reduced the severity of local and systemic inflammation in a murine model of intestinal I/R when given before or after reperfusion injury. These observations suggest that IL-10 may exert its effect by blocking cytokine production and distant organ neutrophil accumulation.