Sakayori S
First Department of Medicine, Kyourin University.
Kansenshogaku Zasshi. 1992 May;66(5):568-78. doi: 10.11150/kansenshogakuzasshi1970.66.568.
This study was performed to demonstrate the role of TNF in septic ARDS. The interaction with neutrophil and TNF was examined in both in vitro and in rat experimental observation. The results obtained are as follows: Serum level of natural TNF was significantly increased immediately after the endotoxin injection into the rat vein. In in vitro observation, TNF activated neutrophil and enhanced super oxide production and elastase was released from neutrophil. On the other hand, TNF was inactivated by contact with elastase released from activated PMNs both in dose and in time dependently. Also, in the in vivo study, the serum level of natural TNF that was enhanced by endotoxin injection was continued for a longer period in neutropenic rats than in the normal rat. The lung tissue injury such as cell infiltration, capillary congestion and increased intrapulmonary fluid in morphometric determination were observed only when the extremely high dose of TNF was injected. These findings were more significantly observed in the neutropenic rats than in the normal neutrophil rat. The weaker interaction of PMNs elastase to TNF is suspected in such neutropenic animals. From the above, the role of TNF in septic ARDS may be explained as follows: By endotoxin injection, TNF is released from stimulated macrophages. The released TNF activates neutrophil which plays the main role of septic ARDS. In the usual system, lung tissue damage induced by TNF is inhibited, because TNF is inactivated by elastase released from activated PMNs. However, in neutropenic state, PMNs elastase is not enough to inhibit the TNF action, then the tissue damage is directly induced by TNF. As my conclusion, the role of TNF in septic ARDS is to provide two different ways by the host is condition. One is to activate neutrophils in the usual condition and the another is to introduce direct damage of lung tissue in the neutropenic state.
本研究旨在阐明肿瘤坏死因子（TNF）在脓毒症急性呼吸窘迫综合征（ARDS）中的作用。在体外实验和大鼠实验观察中，对中性粒细胞与TNF的相互作用进行了研究。获得的结果如下：向大鼠静脉注射内毒素后，血清中天然TNF水平立即显著升高。在体外观察中，TNF激活中性粒细胞，增强超氧化物的产生，中性粒细胞释放弹性蛋白酶。另一方面，TNF与活化的多形核中性粒细胞（PMN）释放的弹性蛋白酶接触后，在剂量和时间上均呈依赖性失活。此外，在体内研究中，内毒素注射后血清中天然TNF水平升高的持续时间，在中性粒细胞减少的大鼠中比正常大鼠更长。仅在注射极高剂量的TNF时，才观察到形态学测定中出现的肺组织损伤，如细胞浸润、毛细血管充血和肺内液体增加。这些发现中性粒细胞减少的大鼠比正常中性粒细胞大鼠更明显。怀疑在这种中性粒细胞减少的动物中，PMN弹性蛋白酶与TNF的相互作用较弱。综上所述，TNF在脓毒症ARDS中的作用可解释如下：通过注射内毒素，TNF从受刺激的巨噬细胞中释放出来。释放的TNF激活中性粒细胞，而中性粒细胞在脓毒症ARDS中起主要作用。在通常情况下，TNF诱导的肺组织损伤受到抑制，因为TNF被活化的PMN释放的弹性蛋白酶失活。然而，在中性粒细胞减少的状态下，PMN弹性蛋白酶不足以抑制TNF的作用，于是TNF直接诱导组织损伤。我的结论是，TNF在脓毒症ARDS中的作用是根据宿主的状况提供两种不同的途径。一种是在正常情况下激活中性粒细胞，另一种是在中性粒细胞减少状态下导致肺组织的直接损伤。
