Silva A T, Bayston K F, Cohen J
Department of Bacteriology, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
J Infect Dis. 1990 Aug;162(2):421-7. doi: 10.1093/infdis/162.2.421.
A monoclonal antibody to recombinant murine tumor necrosis factor-alpha (TNF alpha), TN3-19.12, was used to explore pathogenetic mechanisms and therapeutic strategies in gram-negative shock. In mice receiving an LD90 dose of Escherichia coli O111, TN3-19.12 prevented death if given 1.5 h before or 30 min after challenge. Less protection was conferred if the antibody was given 2.5 h after challenge. In control mice receiving an irrelevant antibody, L2-3D9, TNF alpha levels rose (less than or equal to 185.1 +/- 26.1 ng/ml) by 90 min and had returned to baseline by 5 h. Mice receiving TN3-19.12 did not have this response. TN3-19.12 was of limited benefit in mice receiving Pseudomonas aeruginosa but had no protective effect in cyclophosphamide-treated mice receiving Klebsiella pneumoniae. In L2-3D9-treated mice, TNF alpha levels were elevated to 61.8 +/- 27.9 and 49.7 +/- 5.1 ng/ml by 90 min in the two models, respectively. TNF alpha levels in TN3-19.12-treated mice in these two models were very low (3.9-5.5 ng/ml). TNF alpha is a mediator in gram-negative shock; antibody to TNF alpha can be of value in prophylaxis and treatment, but its clinical use remains to be established.
一种针对重组小鼠肿瘤坏死因子-α（TNFα）的单克隆抗体TN3-19.12，被用于探究革兰氏阴性菌感染性休克的发病机制和治疗策略。在接受致死剂量90%（LD90）的大肠杆菌O111攻击的小鼠中，如果在攻击前1.5小时或攻击后30分钟给予TN3-19.12，可预防死亡。若在攻击后2.5小时给予该抗体，则保护作用较弱。在接受无关抗体L2-3D9的对照小鼠中，TNFα水平在90分钟时升高（≤185.1±26.1纳克/毫升），并在5小时时恢复至基线水平。接受TN3-19.12的小鼠没有这种反应。TN3-19.12对接受铜绿假单胞菌攻击的小鼠益处有限，但对接受环磷酰胺治疗并感染肺炎克雷伯菌的小鼠没有保护作用。在L2-3D9治疗的小鼠中，在两种模型中，TNFα水平在90分钟时分别升高至61.8±27.9和49.7±5.1纳克/毫升。在这两种模型中，接受TN3-19.12治疗的小鼠的TNFα水平非常低（3.9 - 5.5纳克/毫升）。TNFα是革兰氏阴性菌感染性休克的一种介质；抗TNFα抗体在预防和治疗中可能具有价值，但其临床应用仍有待确定。
