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Cytokine modulation with continuous hemodiafiltration for treatment and prevention of multiple organ failure

连续血液透析滤过的细胞因子调节用于治疗和预防多器官衰竭

基本信息

批准号：
11470238
负责人：
HIRASAWA Hiroyuki
金额：
$ 8.96万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

Inflammatory cytokines have been implicated as a key mediator playing an important role in the pathophysiology of multiple organ failure (MOF). This study was undertaken to evaluate the removal of cytokines from the circulation with continuous hemodiafiltration (CHDF) using polymethyl methacrylate membrane (PMMA-CHDF) and the efficacy of PMMA-CHDF in the treatment of sepsis or other critical conditions through such removal of causative mediators. In this study, we found that clearance of cytokines with PMMA-CHDF positively correlates with pre-CHDF blood levels of cytokine : the higher the blood level, the greater the clearance. Furthermore, our data showed that the blood levels of cytokines were significantly decreased with PMMA-CHDF. As for the clinical benefits of cytokine removal, there were positive correlation between changes in blood levels of cytokines with PMMA-CHDF and changes in cellular injury score in MOF patients. In acute respiratory distress syndrome (ARDS), there was a significant and positive correlation between the degree of decrease in blood levels of cytokines and the degree of improvement in respiratory index (RI). Thus these data clearly demonstrated that cytokine removal with PMMA-CHDF was clinically relevant in the critically ill. On the other hand, spontaneous and cytokine-induced apoptosis of circulating polymorphonuclear leukocyte (PMN) wewe greatly decreased in critical conditions such as sepsis and MOF. In contrast, the inhibited circulating PMN apoptosis could lead to be amplified systemic inflammation and organ injury. Therefore, we evaluated whether the removal of cytokines with PMMA-CHDF can modulates circulating PMN apoptosis or not. We investigated the relation between blood levels of cytokines and circulating PMN apoptosis with PMMA-CHDF in organ failure patients. We found that there was a correlation between the degree of decrease in blood levels of interleukin-6 and the degree of improvement in circulating PMN apoptosis.

炎症因子在多器官功能衰竭（MOF）的病理生理中起着重要作用。本研究旨在评估使用聚甲基丙烯酸甲酯膜（PMMA-CHDF）的持续血液滤过（CHDF）去除循环中的细胞因子，以及PMMA-CHDF通过去除致病介质治疗脓毒症或其他危重疾病的疗效。在本研究中，我们发现PMMA-CHDF对细胞因子的清除率与chdf前血液中细胞因子水平呈正相关：血液中细胞因子水平越高，清除率越大。此外，我们的数据显示，PMMA-CHDF显著降低了血液中细胞因子的水平。对于细胞因子去除的临床益处，PMMA-CHDF与MOF患者血液中细胞因子水平的变化与细胞损伤评分的变化呈正相关。急性呼吸窘迫综合征（acute respiratory distress syndrome， ARDS）患者血液中细胞因子水平下降程度与呼吸指数（respiratory index， RI）改善程度呈显著正相关。因此，这些数据清楚地表明，用PMMA-CHDF去除细胞因子在危重患者中具有临床相关性。另一方面，在脓毒症和MOF等危重情况下，循环多形核白细胞（PMN）的自发凋亡和细胞因子诱导的凋亡显著减少。相反，循环PMN凋亡的抑制可导致全身炎症和器官损伤的放大。因此，我们评估了PMMA-CHDF去除细胞因子是否可以调节循环PMN凋亡。我们研究了器官衰竭患者外周血细胞因子水平与循环PMN凋亡及PMMA-CHDF之间的关系。我们发现血液中白细胞介素-6水平的降低程度与循环PMN细胞凋亡的改善程度之间存在相关性。