Barton B E, Jackson J V
Schering-Plough Research Institute, Kenilworth, New Jersey 07033.
Infect Immun. 1993 Apr;61(4):1496-9. doi: 10.1128/iai.61.4.1496-1499.1993.
C57BL/6J mice given low doses of lipopolysaccharide (LPS) (100 ng per mouse) plus D-galactosamine (8 mg per mouse) die within 24 h following LPS administration. We used this septic shock model to confirm the role of tumor necrosis factor in mortality using a monoclonal antibody to tumor necrosis factor to prevent lethality. Furthermore, we demonstrated that interleukin 6, rather than playing a lethal role, protected mice against death in this septic shock model. Antibody to interleukin 6 did not affect the fatal outcome in this low-LPS-dose model. However, pretreatment with antibody to tumor necrosis factor did protect the mice against death, in a dose-dependent manner. Moreover, mortality was enhanced by pretreatment with antibody to interleukin 6 when tumor necrosis factor was partly limited by anti-tumor necrosis factor treatment. Mortality was significantly reduced by pretreatment with both recombinant interleukin 6 and low doses of antibody to tumor necrosis factor; in the absence of the low dose of antibody to tumor necrosis factor, interleukin 6 alone did not confer any protection. These data demonstrate in vivo antagonistic activities of tumor necrosis factor and interleukin 6 and show that interleukin 6 can play a protective role against death from septic shock.
给予低剂量脂多糖（LPS）（每只小鼠100纳克）加D - 半乳糖胺（每只小鼠8毫克）的C57BL / 6J小鼠在LPS给药后24小时内死亡。我们使用这种脓毒症休克模型，通过使用抗肿瘤坏死因子单克隆抗体来预防致死性，以证实肿瘤坏死因子在死亡率中的作用。此外，我们证明白细胞介素6在这种脓毒症休克模型中并非起致死作用，而是保护小鼠免于死亡。抗白细胞介素6抗体在这种低LPS剂量模型中不影响致命结局。然而，用抗肿瘤坏死因子抗体预处理确实以剂量依赖的方式保护小鼠免于死亡。此外，当肿瘤坏死因子被抗肿瘤坏死因子治疗部分限制时，用抗白细胞介素6抗体预处理会增加死亡率。用重组白细胞介素6和低剂量抗肿瘤坏死因子抗体预处理可显著降低死亡率；在没有低剂量抗肿瘤坏死因子抗体的情况下，单独的白细胞介素6没有提供任何保护作用。这些数据证明了肿瘤坏死因子和白细胞介素6在体内的拮抗活性，并表明白细胞介素6可以对脓毒症休克死亡起到保护作用。
