Pretreatment with recombinant murine tumor necrosis factor alpha/cachectin and murine interleukin 1 alpha protects mice from lethal bacterial infection.
Pretreatment with recombinant murine tumor necrosis factor alpha/cachectin and murine interleukin 1 alpha protects mice from lethal bacterial infection.
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DOI：
10.1084/jem.169.6.2021
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发表时间：
1989-06-01
期刊：
影响因子：
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通讯作者：
Gemski P
中科院分区：
文献类型：
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作者：
Cross AS;Sadoff JC;Kelly N;Bernton E;Gemski P
肿瘤坏死因子/恶病素（TNF/C）是细菌内毒素引起的休克和死亡的主要介质。我们发现，C3H/HeJ 小鼠对内毒素产生 TNF/C 的反应能力较弱，其对大肠杆菌致死性感染的敏感性比 TNF 反应性同源小鼠 C3H/HeN 高 1,000 倍。这一令人惊讶的发现表明，这种致命肽也可能参与宿主保护。为了检验这一假设，我们用重组鼠 TNF/C-α 和 IL-1 α 的组合预处理 C3H/HeJ 小鼠。这种组合可以保护这些小鼠免受腹膜内细菌攻击，其细菌浓度超过 20 LD50S（接近 2 x 10(2) CFU），在未治疗的小鼠中，细菌浓度增长至每毫升血液和每克肝脏超过 10(7) CFU 的水平。这表明这些细胞因子在宿主防御需要细菌在宿主内复制的侵入性感染中发挥着重要作用。这些保护机制对于毒性较小的生物体可能并不重要。这些发现可能对建议使用抗 TNF/C 药物治疗感染性休克具有重要意义。
Tumor necrosis factor/cachectin (TNF/C) is the principal mediator of bacterial endotoxin-induced shock and death. We found that the C3H/HeJ mouse, which is less able to produce TNF/C in response to endotoxin, has a 1,000-fold greater susceptibility to lethal infection with Escherichia coli than the TNF-responsive congenic mouse, C3H/HeN. This surprising finding suggested that this lethal peptide may also be involved in host protection. To test this hypothesis we pretreated the C3H/HeJ mouse with a combination of recombinant murine TNF/C-alpha and IL-1 alpha. This combination protected these mice against an intraperitoneal bacterial challenge of greater than 20 LD50S (nearly 2 x 10(2) CFU) that grew to a level of greater than 10(7) CFU/ml of blood and per gram of liver in untreated mice. This suggests a significant role for these cytokines in host defenses against invasive infections that require bacterial replication within the host. These protective mechanisms may not be important for less virulent organisms. These findings may have important implications for the proposed use of anti- TNF/C agents in the treatment of septic shock.