ter Steege J C, van de Ven M W, Forget P P, Brouckaert P, Buurman W A
Department of Pediatrics, Academic Hospital Maastricht, The Netherlands.
Cytokine. 1998 Feb;10(2):115-23. doi: 10.1006/cyto.1997.0263.
Mice injected with lipopolysaccharide (LPS) develop lethal septic shock, accompanied by elevated serum NOx, interferon gamma (IFN-gamma), tumour necrosis factor alpha (TNF-alpha) and TNF-receptor levels. Elevated NO levels are thought to play a central role in tissue damage observed during septic shock. In vitro data indicate that IFN-gamma and TNF-alpha play an important role in LPS-induced NO release. Further, interleukin 10 (IL-10) has been shown to inhibit the release of pro-inflammatory cytokines such as IFN-gamma and TNF-alpha. Therefore, in the present study, we investigated the role of IFN-gamma, TNF-alpha, and IL-10 in LPS-induced NO release. To this end, mice were pretreated with anti-IFN-gamma, anti-TNF-alpha, anti-IL-10 mAbs or combinations of these 2 h before LPS-challenge. The results indicate that IFN-gamma, TNF-alpha as well as IL-10 are involved in the regulation of LPS-induced NO release. Blocking either IFN-gamma or TNF-alpha has no effect on LPS-induced NO release, however, blocking both IFN-gamma and TNF-alpha nearly completely prevents NO release after LPS challenge, suggesting that the presence of either TNF-alpha or IFN-gamma is essential for induction of NO release after LPS challenge. Further, the results obtained with anti-IL-10 treatment suggest the presence of an IL-10 inducible factor which together with IFN-gamma and TNF-alpha regulates LPS-induced NO release.
注射脂多糖（LPS）的小鼠会发生致死性脓毒性休克，同时伴有血清氧化氮（NOx）、干扰素γ（IFN-γ）、肿瘤坏死因子α（TNF-α）和TNF受体水平升高。NO水平升高被认为在脓毒性休克期间观察到的组织损伤中起核心作用。体外数据表明，IFN-γ和TNF-α在LPS诱导的NO释放中起重要作用。此外，白细胞介素10（IL-10）已被证明可抑制促炎细胞因子如IFN-γ和TNF-α的释放。因此，在本研究中，我们研究了IFN-γ、TNF-α和IL-10在LPS诱导的NO释放中的作用。为此，在LPS攻击前2小时，用抗IFN-γ、抗TNF-α、抗IL-10单克隆抗体或这些抗体的组合对小鼠进行预处理。结果表明，IFN-γ、TNF-α以及IL-10参与了LPS诱导的NO释放的调节。阻断IFN-γ或TNF-α对LPS诱导的NO释放没有影响，然而，同时阻断IFN-γ和TNF-α几乎完全阻止了LPS攻击后NO的释放，这表明TNF-α或IFN-γ的存在对于LPS攻击后诱导NO释放至关重要。此外，抗IL-10治疗获得的结果表明存在一种IL-10诱导因子，其与IFN-γ和TNF-α一起调节LPS诱导的NO释放。
