Endogenous interferon-γ induced by bacterial lipopolysaccbaride ; its production mechanism and roles as a mediator

宿主对细菌脂多糖（LPS）的反应是由多种介质如肿瘤坏死因子（TNF）、白细胞介素(IL)-6和一氧化氮（NO）的产生介导的。干扰素(IFN)-γ在免疫系统中起着重要作用，注射LPS的动物体内血清中可检测到干扰素-γ，但其体外诱导机制及其作为LPS介质的作用尚不清楚。培养小鼠腹膜渗出细胞（PEC），用LPS刺激其诱导介质。在抗ifn -γ存在的情况下，PEC培养中NO的产生明显受到抑制，但TNF和IL-6的产生几乎没有受到抑制。除了抗IFN-γ外，我们还检测了多种抗LPS介质的抗体，发现抗il -12和抗il -18对LPS诱导的NO和IFN-γ的产生有抑制作用，并且这些抗体协同作用表现出较强的抑制作用。这些细胞因子，被称为IFN-γ诱导细胞因子，协同刺激PEC产生IFN-γ和NO。作为贴壁细胞制备的PEC中的巨噬细胞群体对LPS产生IL-12反应良好，但对产生IFN-γ和NO反应较弱。巨噬细胞也对IFN-γ产生NO反应良好。为了通过LPS或IL12+IL18刺激产生IFN-γ，需要PEC培养中的非贴壁细胞。综上所述，巨噬细胞通过产生IL-12和IL-18等中间体，刺激非贴壁细胞产生IFN-γ的途径在lps诱导的IFN-γ产生中起主要作用，IFN-γ主要促进巨噬细胞产生NO，但很少产生TNF和IL-6。

Host responses to bacterial lipopolysaccharide (LPS) are mediated by production of various mediators such as tumor necrosis factor (TNF), interleukin (IL)-6 and nitric oxide (NO). Interferon (IFN)-γ, which plays important roles in immune system, is detectable in vivo in the sera of LPS-injected animals but its induction mechanisms by LPS in vitro and its roles as an LPS mediator have not been well understood.Mouse peritoneal exudate cells (PEC) were cultured and stimulated with LPS for induction of mediators. In the presence of anti-IFN-γ, NO production in the PEC culture was remarkably suppressed but production of TNF and IL-6 was scarcely suppressed. Besides anti-IFN-γ, various antibodies against LPS mediators were examined and found that anti-IL-12 and anti-IL-18 showed suppressivc effect on LPS-induced production of NO and IFN-γ, and that these antibodies in synergy showed strong suppression. These cytokines, known as IFN-γ-inducing cytokines, stimulated in synergy the PEC for production of IFN-γ and NO. Macrophage population in the PEC prepared as adherent cells responded well to LPS for IL-12 production but weakly for production of IFN-γ and NO. The macrophages also responded well to IFN-γ for NO production. For production of IFN-γ by stimulation with LPS or IL12+IL18, non-adherent cells in the PEC culture were required. Considering these results all together, a pathway trough the production of intermediates such as IL-12 and IL-18 by macrophages that stimulate non-adherent cells for production of IFN-γ was revealed to play a main role in the LPS-induced IFN-γ production and the IFN-γ contributed largely to production of NO by macrophages but scarcely to production of TNF and IL-6.