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

1)环境和氧分压变化对细胞功能的影响：我们在不同温度下将人全血与脂多糖(LPS)共同孵育，发现低氧和高氧都能抑制白细胞介素8(IL-8)的产生。然后，我们将人脐静脉内皮细胞(HUVEC)暴露在不同的氧分压下，检测细胞功能的变化。在高氧条件下，内毒素刺激后IL-8mRNA的表达明显加快，而磷酸化JNK的表达明显增加。此外，当在不同条件下用CCD摄像机连续监测HUVEC时，这些细胞以相同的方式移动，无论是否存在内毒素、肿瘤坏死因子或高氧。然而，只有当人脐静脉内皮细胞在肿瘤坏死因子和高氧的共同存在下培养时，大多数细胞才最终死亡。2)高温和烧伤患者的病理生理学：在高温…沐浴后意识水平改变的患者严重烧伤患者血清IL-6、IL-8、IL-10水平异常升高，而严重烧伤患者IL-18水平降低。我们接下来分析了50例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SIRS患者的凝血/纤溶和中性粒细胞弹性蛋白酶相关因子，发现D-二聚体与TAT、PIC、e-XDP显著相关。ARDS患者血清纤维蛋白原、D-二聚体弹力酶/α1-AT复合体、e-XDP水平升高。3)烧伤后小鼠免疫状态的改变及其药理正常化：我们建立了30%Ⅲ度皮肤烧伤小鼠模型，发现烧伤后肝脏IL-18含量明显下降。在这些小鼠中，在亚致死剂量的内毒素攻击后，小鼠的存活率显著降低，而补充IL-18显著改善了内毒素攻击后小鼠的存活率，并增加了脾细胞产生MIP-2的能力。较少

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