Simpson S Q, Casey L C
Department of Pulmonary Medicine, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois.
Crit Care Clin. 1989 Jan;5(1):27-47.
TNF is a small protein secreted by activated monocytes and macrophages that mediates the in vivo effects of endotoxin. When injected into experimental animals, TNF reproduces the picture of septic or endotoxin shock. In addition, antibodies to TNF protect animals against the deleterious effects of IV injections of either LPS or live bacteria. Specifically, the available evidence suggests that TNF may be necessary for the organ injury and failure seen in sepsis. However, TNF probably is not the final common pathway to shock and tissue injury. Inhibition of cyclooxygenase is protective from the lethal effects of both LPS and TNF infusion, suggesting that prostanoids play an important, and perhaps more proximal role in the generation of tissue injury. In addition, TNF is produced and cleared from the blood-stream within a short period of time after an LPS stimulus, suggesting that TNF sets into motion a chain of events that may be self-perpetuating even in the absence of further TNF stimulus. In the near future, the treatment of sepsis may involve the administration of antibodies both to TNF and to LPS. Cyclooxygenase inhibitors should also begin to play a role in the therapy of sepsis. In the more distant future it is likely that we will be able to manipulate the state of activation of genes that code for TNF to exert some control over its production and secretion. It is perhaps within our grasp to finally reduce the morbidity and mortality of this lethal condition.
肿瘤坏死因子（TNF）是一种由活化的单核细胞和巨噬细胞分泌的小蛋白，它介导内毒素的体内效应。当将TNF注射到实验动物体内时，它会重现败血症或内毒素休克的症状。此外，针对TNF的抗体可保护动物免受静脉注射脂多糖（LPS）或活菌的有害影响。具体而言，现有证据表明TNF可能是败血症中出现器官损伤和功能衰竭所必需的。然而，TNF可能并非导致休克和组织损伤的最终共同途径。抑制环氧化酶可保护动物免受LPS和TNF输注的致死效应，这表明前列腺素在组织损伤的发生中起重要作用，而且可能是更直接的作用。此外，在LPS刺激后短时间内，TNF在血流中产生并清除，这表明TNF引发了一系列事件，即使在没有进一步TNF刺激的情况下，这些事件也可能自我持续。在不久的将来，败血症的治疗可能包括给予针对TNF和LPS的抗体。环氧化酶抑制剂也应开始在败血症治疗中发挥作用。在更遥远的将来，我们很可能能够操纵编码TNF的基因的激活状态，以对其产生和分泌进行某种控制。最终降低这种致命疾病的发病率和死亡率或许是我们力所能及的。
