Wayte J, Silva A T, Krausz T, Cohen J
Department of Infectious Diseases and Bacteriology, Hammersmith Hospital, London, UK.
Crit Care Med. 1993 Aug;21(8):1207-12. doi: 10.1097/00003246-199308000-00022.
To examine the effect of a monoclonal antibody to tumor necrosis factor-alpha (TNF-alpha) in a murine model of shock due to Streptococcus pyogenes.
Prospective, multiexperimental, randomized, controlled trial.
University hospital research laboratory.
An LD90 murine model of Gram-positive shock using S. pyogenes, associated with the presence of significant concentrations of TNF-alpha in the circulation. Prophylactic administration of antibody with concomitant saline controls. A 500-micrograms TN3-19.12 (hamster monoclonal antibody to recombinant murine TNF), or saline, by intravenous injection was administered.
Administration of 0.3 mL of 6 x 10(8) colony-forming units/mL of S. pyogenes H250 to mice resulted in 90% to 100% mortality rates in 72 hrs. Serum TNF-alpha concentrations peaked at 2 hrs after bacterial challenge and were 67.7 +/- 18.6 ng/mL. Treatment with anti-TNF-alpha monoclonal antibody abolished the serum TNF-alpha concentrations but did not affect the mortality rate. Serum endotoxin concentrations were < 50 pg/mL before challenge and at 0.5, 1, 2, 5, and 24 hrs after challenge.
Pretreatment with an anti-TNF monoclonal antibody was not protective in this model of S. pyogenes sepsis, despite the presence of significant amounts of TNF in the circulation. These data suggest that TNF-alpha may not play such a crucial role in the pathogenesis of shock due to S. pyogenes.
在化脓性链球菌所致休克的小鼠模型中研究抗肿瘤坏死因子-α（TNF-α）单克隆抗体的作用。
前瞻性、多实验、随机、对照试验。
大学医院研究实验室。
使用化脓性链球菌建立革兰氏阳性休克的LD90小鼠模型，该模型伴有循环中存在高浓度的TNF-α。预防性给予抗体并设置生理盐水对照。通过静脉注射给予500微克TN3-19.12（抗重组鼠TNF的仓鼠单克隆抗体）或生理盐水。
给小鼠注射0.3毫升浓度为6×10⁸菌落形成单位/毫升的化脓性链球菌H250，72小时内死亡率达90%至100%。血清TNF-α浓度在细菌攻击后2小时达到峰值，为67.7±18.6纳克/毫升。用抗TNF-α单克隆抗体治疗可消除血清TNF-α浓度，但不影响死亡率。攻击前及攻击后0.5、1、2、5和24小时血清内毒素浓度<50皮克/毫升。
在该化脓性链球菌败血症模型中，抗TNF单克隆抗体预处理无保护作用，尽管循环中存在大量TNF。这些数据表明TNF-α在化脓性链球菌所致休克的发病机制中可能并非起关键作用。
