Hart P H, Whitty G A, Piccoli D S, Hamilton J A
Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Immunology. 1989 Mar;66(3):376-83.
There have been suggestions that the production of pro-inflammatory mediators by human monocytes in response to interferon-gamma (IFN-gamma) may be controlled by changes in prostaglandins. Therefore we investigated tumour necrosis factor alpha (TNF alpha) and interleukin-1 (IL-1) activities and prostaglandin E2 (PGE2) levels in the supernatants of highly purified human monocytes cultured for 18 hr with recombinant human IFN-gamma. IFN-gamma (100 U/ml) did not stimulate monocytes isolated by counter-current centrifugal elutriation for detectable TNF alpha or IL-1 activities, or PGE2 production. However, IFN-gamma synergistically enhanced lipopolysaccharide (LPS)-induced TNF alpha and IL-1 activities. In contrast, there was no consistent change in PGE2 levels upon addition of IFN-gamma to LPS-treated monocyte cultures. The TNF alpha and IL-1 activities induced by LPS and by LPS with IFN-gamma were reduced by PGE2, and stimulated by indomethacin. As reported previously for IL-1 activities, the regulation by cyclo-oxygenase products of TNF alpha activities reflected predominantly a control of the production of immunoreactive TNF alpha, rather than the measurement of TNF alpha bio-activity. However, the addition of indomethacin or PGE2 to monocyte cultures did not change the extent of IFN-gamma synergy with LPS for increased TNF alpha and IL-1 activities. The results of this study suggest that, despite control by cyclo-oxygenase products of TNF alpha and IL-1 production in human monocytes, IFN-gamma may enhance TNF alpha and IL-1 activities independently of this regulatory mechanism. These findings are contrary to those suggested for the regulation by prostanoids of IL-1 production by murine macrophages.
有人提出，人类单核细胞对干扰素-γ（IFN-γ）产生的促炎介质可能受前列腺素变化的控制。因此，我们研究了用重组人IFN-γ培养18小时的高度纯化人单核细胞上清液中的肿瘤坏死因子α（TNFα）和白细胞介素-1（IL-1）活性以及前列腺素E2（PGE2）水平。IFN-γ（100 U/ml）未刺激通过逆流离心淘析分离的单核细胞产生可检测到的TNFα或IL-1活性，也未刺激PGE2的产生。然而，IFN-γ协同增强脂多糖（LPS）诱导的TNFα和IL-1活性。相比之下，向LPS处理的单核细胞培养物中添加IFN-γ后，PGE2水平没有一致的变化。LPS和LPS与IFN-γ诱导的TNFα和IL-1活性被PGE2降低，并被吲哚美辛刺激。如先前报道的IL-1活性一样，TNFα活性受环氧化酶产物的调节主要反映了对免疫反应性TNFα产生的控制，而不是TNFα生物活性的测量。然而，向单核细胞培养物中添加吲哚美辛或PGE2并没有改变IFN-γ与LPS协同增加TNFα和IL-1活性的程度。本研究结果表明，尽管人类单核细胞中TNFα和IL-1的产生受环氧化酶产物的控制，但IFN-γ可能独立于这种调节机制增强TNFα和IL-1活性。这些发现与前列腺素对小鼠巨噬细胞IL-1产生的调节作用相反。
