PROTECTIVE ROLE OF INTERLEUKIN-6 IN THE LIPOPOLYSACCHARIDE-GALACTOSAMINE SEPTIC SHOCK MODEL
PROTECTIVE ROLE OF INTERLEUKIN-6 IN THE LIPOPOLYSACCHARIDE-GALACTOSAMINE SEPTIC SHOCK MODEL
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DOI：
10.1128/iai.61.4.1496-1499.1993
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发表时间：
1993-04-01
影响因子：
3.1
通讯作者：
JACKSON, JV
中科院分区：
文献类型：
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作者：
BARTON, BE;JACKSON, JV
给予低剂量脂多糖（LPS）（每只小鼠100 ng）加D-半乳糖胺（每只小鼠8 mg）的C57 BL/6 J小鼠在LPS施用后24小时内死亡。我们使用这种感染性休克模型来证实肿瘤坏死因子在死亡率中的作用，使用肿瘤坏死因子的单克隆抗体来防止致死性。此外，我们证明了白细胞介素6，而不是发挥致命的作用，保护小鼠免于死亡，在这个脓毒性休克模型。白细胞介素6抗体在低剂量LPS模型中不影响致死性结局。然而，用肿瘤坏死因子抗体预处理确实以剂量依赖性方式保护小鼠免于死亡。此外，当肿瘤坏死因子部分受到抗肿瘤坏死因子治疗的限制时，白细胞介素6抗体预处理可提高死亡率。通过重组白细胞介素6和低剂量肿瘤坏死因子抗体预处理，死亡率显著降低;在没有低剂量肿瘤坏死因子抗体的情况下，单独使用白细胞介素6没有任何保护作用。这些数据证明了肿瘤坏死因子和白细胞介素6的体内拮抗活性，并表明白细胞介素6可以对感染性休克的死亡起到保护作用。
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.