THE INFLUENCE OF FLUID ADMINISTRATION ON THE EFFECTS OF TUMOR NECROSIS FACTOR SOL

尽管在临床前研究中取得了令人鼓舞的结果，但迄今为止，在脓毒症患者中使用顺铂的临床经验令人失望。肿瘤坏死因子可溶性受体（TNFsr）就是这样一种试剂。在利用内毒素或革兰氏阴性菌输注挑战的早期临床前工作中，TNFsr具有保护作用并改善存活率。这种保护似乎与TNFsr改善心血管功能有关。然而，在临床脓毒症试验中，这种药物并不是有益的，在某些情况下似乎是有害的。这些发现表明，在临床前研究中未确定的因素可能改变了TNFsr在临床研究中的作用。一个这样的因素可能是存在或缺乏其他支持疗法。在临床而非临床前研究中，受试者还通过液体给药进行心血管支持。在临床研究中存在这样的支持可能否定了TNFsr对心血管功能的有益作用，并可能加重其对宿主防御的不利影响。在本研究中，使用多因素设计，我们正在测试的影响，输液对TNFsr与血管内和血管外感染的大鼠模型脓毒症。

Despite encouraging results in preclinical studies, clinical experience with antiinflammatory in patients with sepsis have been disappointing to date. Tumor necrosis factor soluble receptor (TNFsr) is one such agent. In early preclinical work utilizing endotoxin or gram-negative bacteria infusion challenges, TNFsr was protective and improved survival. This protection appeared to be related in part to improvements in cardiovascular function with TNFsr. However, in clinical sepsis trials this agent was not beneficial and in some cases appeared to harmful effects. These finding suggest that factors not identified in preclinical studies may have altered the effects of TNFsr in clinical studies. One such factor may be the presence or absence of other supportive therapies. In clinical but not preclinical studies, subjects also have cardiovascular support with fluid administration. The presence of such support in clinical studies may have negated the beneficial effects of TNFsr on cardiovascular function and possibly accentuated adverse effects it may have had on host defense. In the present study, using a multifactorial design, we are testing the effects of fluid administration on TNFsr with both intravascular and extravascular infection in a rat model of sepsis.