Vascular endothelial growth factor blockade reduces plasma cytokines in a murine model of polymicrobial sepsis
Vascular endothelial growth factor blockade reduces plasma cytokines in a murine model of polymicrobial sepsis
复制标题
DOI：
10.1007/s10753-004-6050-3
复制
发表时间：
2004-10-01
期刊：
影响因子：
5.1
通讯作者：
Gold, JA
中科院分区：
文献类型：
--
作者：
Nolan, A;Weiden, MD;Gold, JA
许多细胞因子，包括血管内皮生长因子(VEGF)，参与了脓毒症的发病机制。虽然血管内皮生长因子的过度表达会导致肺毛细血管渗漏，但血管内皮生长因子在脓毒症中的作用尚不清楚。我们利用血管内皮生长因子陷阱(VEGF(T))对脓毒症患者的血管内皮生长因子进行了研究。盲肠结扎穿孔(CLP)诱导C57BL/6小鼠发生多菌败血症，血浆血管内皮生长因子水平显著升高(234pg/mLvs.46pg/m L；p=0.03)。抑制血管内皮生长因子对死亡率或肺渗漏无影响，但可降低血浆IL-6(120vs.236 ng/mL；p=0.02)和IL-10(16vs.41 ng/mLp=0.03)。这些炎性细胞因子的改变与主要的负性抑制C/EBPβ水平升高有关。在体外，血管内皮生长因子刺激巨噬细胞IL-6、IL-10，并降低巨噬细胞C/EBPβ抑制亚型。综上所述，这些数据表明，血管内皮生长因子可以通过调节C/EBPβ来调节小鼠多菌败血症中炎性细胞因子的产生。
Numerous cytokines, including vascular endothelial growth factor (VEGF), are implicated in the pathogenesis of sepsis. While overexpression of VEGF produces pulmonary capillary leak, the role of VEGF in sepsis is less clear. We investigated VEGF in sepsis, utilizing a VEGF trap (VEGF(T)). Polymicrobial sepsis was induced in C57BL/6 mice by cecal ligation and puncture (CLP) and resulted in significantly increased plasma VEGF levels (234 vs. 46 pg/mL; p = 0.03). Inhibition of VEGF had no effect on mortality or lung leak but did attenuate plasma IL-6 (120 vs. 236 ng/mL; p = 0.02) and IL-10 (16 vs. 41 ng/mL; p = 0.03). These alterations in inflammatory cytokines were associated with increased levels of the dominant negative inhibitory C/EBP beta. In vitro, VEGF stimulated IL-6, IL-10 and reduced the inhibitory isoform of C/EBP beta in cultured macrophages. Together these data suggest VEGF can regulate inflammatory cytokine production in murine polymicrobial sepsis, via regulation of C/EBP beta.