权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Analysis of altered immunological responses under abnormal environmental conditions, including environmental temperature, and the trial of its active modulation for the treatment of critically ill patients

环境温度等异常环境条件下免疫反应变化的分析及其主动调节治疗重症患者的尝试

基本信息

批准号：
14370364
负责人：
AIKAWA Naoki
金额：
$ 9.54万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

1)Effect of environmental and oxygen tension changes on cellular functions : We incubated human whole blood with lipopolysaccharide (LPS) at various temperatures and found that both hypoxia and hyperoxia inhibited the production of interleukin-8 (IL-8).We next exposed human umbilical vein endothelial cells (HUVEC) to different oxygen tensions and examined the changes in cellular functions. The expression of IL-8 mRNA after LPS stimulation was accelerated under hyperoxia, which was preceded by the significant increase in phospho-JNK. Furthermore, when HUVECs were continually monitored with CCD cameras under various conditions, these cells moved around in the same manner, irrespective of the presence of LPS, TNF, or hyperoxia. However, only when HUVECs were cultured under the co-presence of TNF and hyperoxia, most cells finally died.2)Pathophysiology of patients under hyperthermia and burn injuries : In patients suffered from altered level of consciousness after bathing with high tempera … More ture, serum levels of IL-6, IL-8, IL-10 were abnormally high and in patients with major burn injuries the plasma levels of IL-18 was lower in patients. We next analyzed plasma cytokines and HGF in 50 SIRS patients and found their increase as well as relative independence of HGF from other cytokines. Finally, we analyzed coagulation/fibrinolysis and neutrophil elastase-related factors in 64 SIRS patients and found a significant correlation between D dimer and TAT, PIC, e-XDP. In ARDS patients, serum levels of fibrinogen, D dimer elastase/alpha 1-AT complex, e-XDP were increased.3)Altered immunological status after burn injury and its pharmacological normalization in mice : We developed a mouse model of 30% third degree skin burn and found a significant decrease in hepatic IL-18 contents after burn injury. In these mice, survival after a sublethal dose of LPS challenge were significantly lowered and IL-18 supplementation significantly ameliorated the survival as well as augmented MIP-2 production by splenic cells after LPS challenge. Less

1)环境和氧分压变化对细胞功能的影响：我们用脂多糖（LPS）在不同温度下孵育人全血，发现缺氧和高氧均抑制白细胞介素-8（IL-8）的产生，然后将人脐静脉内皮细胞（HUVEC）暴露于不同的氧分压下，观察细胞功能的变化。LPS刺激后，高氧下IL-8 mRNA的表达加速，这是由磷酸化JNK的显着增加。此外，当在各种条件下用CCD相机连续监测HUVEC时，这些细胞以相同的方式四处移动，而不管LPS、TNF或高氧的存在。然而，只有在TNF和高氧共同存在的情况下，HUVECs才最终死亡。2）高温和烧伤患者的病理生理：高温浴后意识水平改变的患者， ...更多信息烧伤患者血清IL-6、IL-8、IL-10水平异常增高，严重烧伤患者IL-18水平较低。我们接下来分析了50名SIRS患者的血浆细胞因子和HGF，发现它们的增加以及HGF与其他细胞因子的相对独立性。最后，我们分析了64例SIRS患者的凝血/纤溶和中性粒细胞弹性蛋白酶相关因素，发现D二聚体与达特、PIC、e-XDP显著相关。3）烧伤后小鼠免疫状态的改变及其药理学恢复：我们建立了一种30% Ⅲ度皮肤烧伤的小鼠模型，发现烧伤后肝脏IL-18含量显著降低。在这些小鼠中，在亚致死剂量的LPS攻击后的存活率显著降低，并且IL-18补充显著改善了存活率以及增强了LPS攻击后脾细胞的MIP-2产生。少