BLOCKADE OF TUMOR-NECROSIS-FACTOR REDUCES LIPOPOLYSACCHARIDE LETHALITY, BUT NOT THE LETHALITY OF CECAL LIGATION AND PUNCTURE
BLOCKADE OF TUMOR-NECROSIS-FACTOR REDUCES LIPOPOLYSACCHARIDE LETHALITY, BUT NOT THE LETHALITY OF CECAL LIGATION AND PUNCTURE
复制标题
DOI：
10.1097/00024382-199508000-00002
复制
发表时间：
1995-08-01
期刊：
影响因子：
3.1
通讯作者：
WOLLENBERG, G
中科院分区：
文献类型：
--
作者：
REMICK, D;MANOHAR, P;WOLLENBERG, G
抑制肿瘤坏死因子（TNF）的生物活性在几种脓毒症动物模型中提供了保护。我们研究了在CD-1或BALB\c小鼠中抑制TNF是否可以改善致死性脂多糖（LPS）或盲肠结扎穿孔（CLP）后的存活率。通过在静脉内（i. v.）LPS（600 μ g）。植入式无线电发射器用于连续监测温度。未观察到死亡率降低，抗TNF未能阻止体温下降。在LPS（200 μ g）之前注射抗血清的BALB/c小鼠中，死亡率降低（死亡/总死亡：对照血清，14/14;抗TNF，4/12; p = 0.007对照血清vs.抗TNF）。CD-1小鼠用抗TNF或对照血清预处理; CLP后给予抗生素。抗肿瘤坏死因子并没有减少肺中性粒细胞隔离，提高生存率，或防止败血症发展中观察到的体温下降。在BALB\c小鼠中使用抗生素加抗TNF抗血清进行CLP，但未观察到保护作用。我们的研究结果表明，抗TNF治疗预防LPS死亡率只有当使用某些品系的小鼠和抑制TNF不能降低死亡率在一个更临床相关的脓毒症模型。
Inhibition of tumor necrosis factor (TNF) bioactivity has afforded protection in several animal models of sepsis. We examined whether inhibition of TNF could improve survival after lethal lipopolysaccharide (LPS) or cecal ligation and puncture (CLP) in CD-1 or BALB\c mice. Neutralizing rabbit anti-TNF antisera were evaluated in CD-1 mice by injecting the antisera 3 h before intravenous (i.v.) LPS (600 mu g). Implantable radiotransmitters were used for continuous monitoring of temperature. No decrease in mortality was observed, and the anti-TNF failed to prevent the drop in temperature. In BALB\c mice injected with antisera before LPS (200 mu g) mortality was reduced (dead/total: control sera, 14/14; anti-TNF, 4/12; p = .007 control sera vs. anti-TNF). CD-1 mice were pretreated with anti-TNF or control sera; CLP was performed followed by administration of antibiotics. Anti-TNF did not decrease pulmonary neutrophil sequestration, improve survival, or prevent the decrease in temperature observed as sepsis developed. CLP was performed in the BALB\c mice using antibiotics plus anti-TNF antisera, but no protection was observed. Our results demonstrate that anti-TNF treatment prevents LPS mortality only when using certain strains of mice and inhibition of TNF fails to reduce mortality in a more clinically relevant model of sepsis.