Evans T, Carpenter A, Silva A, Cohen J
Department of Infectious Diseases and Bacteriology, Royal Postgraduate Medical School, London, United Kingdom.
Infect Immun. 1992 Oct;60(10):4133-9. doi: 10.1128/iai.60.10.4133-4139.1992.
To investigate the stimuli required for the induction of nitric oxide synthase (NOS) in sepsis, we have analyzed the levels of this enzyme in the livers of mice infected with a 90% lethal dose of Escherichia coli in a model of gram-negative sepsis. Hepatic NOS levels are markedly induced in this model, with peak values occurring 12 to 22 h following infection. Treatment with TN3-19.12, a neutralizing monoclonal antibody to tumor necrosis factor alpha (TNF-alpha), resulted in complete protection from death in this model of sepsis but had no significant effect on the level of induction of hepatic NOS. Treatment with H22, a monoclonal antibody to gamma interferon (IFN-gamma), also gave significant protection against death and, in addition, did lead to a decrease in the level of induction of the hepatic NOS. Treatment of mice with pure TNF-alpha (0.2 microgram), IFN-gamma (2,000 U), or a combination of the two did not induce the hepatic NOS, but treatment with the combination led to significant mortality (probability of survival at 22 h, 0.32). Thus, the level of induction of NOS within the liver either in sepsis or by the coadministration of TNF-alpha and IFN-gamma does not correlate with death.
为研究脓毒症中诱导一氧化氮合酶（NOS）所需的刺激因素，我们在革兰氏阴性脓毒症模型中，分析了感染90%致死剂量大肠杆菌的小鼠肝脏中该酶的水平。在此模型中，肝脏NOS水平显著升高，感染后12至22小时达到峰值。用TN3 - 19.12（一种针对肿瘤坏死因子α（TNF-α）的中和单克隆抗体）治疗，可使该脓毒症模型中的小鼠完全免受死亡威胁，但对肝脏NOS的诱导水平无显著影响。用H22（一种针对γ干扰素（IFN-γ）的单克隆抗体）治疗，同样能显著保护小鼠免于死亡，此外，还能使肝脏NOS的诱导水平降低。用纯TNF-α（0.2微克）、IFN-γ（2000单位）或两者联合处理小鼠，均不会诱导肝脏NOS，但联合处理会导致显著的死亡率（22小时存活概率为0.32）。因此，脓毒症时或联合给予TNF-α和IFN-γ时肝脏中NOS的诱导水平与死亡无关。
