IL-10 regulates thrombus-induced vein wall inflammation and thrombosis.

IL-10 regulates thrombus-induced vein wall inflammation and thrombosis.
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DOI:
10.4049/jimmunol.161.3.1471
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发表时间:
1998-08
影响因子:
4.4
通讯作者:
L. Downing;R. Strieter;A. Kadell;C. Wilke;J. Austin;B. Hare;M. Burdick;L. Greenfield;T. Wakefield
L. Downing;R. Strieter;A. Kadell;C. Wilke;J. Austin;B. Hare;M. Burdick;L. Greenfield;T. Wakefield
中科院分区:
医学2区
文献类型:
--
作者:
L. Downing;R. Strieter;A. Kadell;C. Wilke;J. Austin;B. Hare;M. Burdick;L. Greenfield;T. Wakefield

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与静脉血栓形成相关的静脉壁炎症是由促炎分子与抗炎分子的失衡所介导的。我们假设IL-10是一种重要的抗炎细胞因子,在静脉血栓形成过程中影响静脉壁炎症和血栓扩散。为了验证这一假设,我们使用了一个下腔静脉血栓形成的模型。于血栓诱导后2天处死动物,进行白细胞形态计量学、髓过氧化物酶活性、静脉壁通透性、血栓重量和静脉壁IL-10的酶联免疫吸附分析。静脉血栓形成时静脉壁IL-10水平升高。中和IL-10会增加炎症,而补充rIL-10则显示出剂量和时间依赖性的炎症减轻。有趣的是,在血栓形成开始时给予2.5微克的低剂量rIL-10最显著地减少了炎症。通过重组IL-10,血栓重量显著减轻。这些研究支持了IL-10在血栓相关炎症和血栓形成的调节中的重要作用,并提示IL-10可以作为治疗静脉血栓的药物。
Vein wall inflammation associated with venous thrombosis is mediated by an imbalance in proinflammatory as compared with antiinflammatory molecules. We hypothesize that IL-10 is an important antiinflammatory cytokine that influences vein wall inflammation and thrombus propagation during venous thrombosis. To test this hypothesis a model of inferior vena caval thrombosis was used. Studies were performed at sacrifice 2 days after thrombus induction and included leukocyte morphometrics, myeloperoxidase activity, vein wall permeability, thrombus weight, and IL-10 ELISA analysis from the vein wall. IL-10 was elevated in the vein wall during venous thrombosis. Neutralization of IL-10 increased inflammation, while supplementation with rIL-10 demonstrated a dose- and time-dependent decrease in inflammation. Interestingly, a low 2.5-microg rIL-10 dose given at time of initiation of thrombosis most significantly decreased inflammation. Thrombus weight was importantly diminished by reconstitution of IL-10. These studies support an important role for IL-10 in the regulation of thrombus-associated inflammation and thrombosis and suggest that IL-10 could be used as a therapeutic agent in the treatment of venous thrombosis.