Luttmann W, Herzog V, Matthys H, Thierauch K H, Virchow J C, Kroegel C
Department of Pneumology, Medical University Clinics, Freiburg, Germany.
Cytokine. 1999 Feb;11(2):127-33. doi: 10.1006/cyto.1998.0410.
In a previous study, we reported that cicaprost, a stable prostacyclin analogue can inhibit the release of granulocyte-macrophage colony-stimulating factor (GM-CSF) from activated human peripheral mononuclear blood cells (PBMCs). Since interleukin (IL-4) and IL-13 have been shown to inhibit the release of cytokines from PBMCs we tested the hypothesis that prostacyclin in combination with IL-4 or IL-13 can act synergistically to modulate the release of IL-10, generally associated with anti-inflammatory properties, and the pro-inflammatory cytokine tumour necrosis factor alpha (TNF-alpha). For this purpose, PBMCs were isolated over Ficoll, stimulated with lipopolysaccharide (LPS) and incubated in the presence of cicaprost, IL-4 or IL-13. There was a significant reduction in TNF-alpha as well as IL-10 secretion from LPS-stimulated PBMCs following incubation with IL-4 or IL-13. In contrast, cicaprost reduced the secretion of TNF-alpha but led to a slight enhancement of IL-10 release from PBMCs. When LPS-activated PBMCs were incubated in the presence of cicaprost and IL-4 or IL-13 there was a selective, synergistic inhibition of the TNF-alpha release which was not observed for IL-10. Thus, our data suggest that prostacyclin can synergize with cytokines to selectively inhibit the release of pro-inflammatory cytokines from PBMCs.
在之前的一项研究中，我们报道了西卡前列素（一种稳定的前列环素类似物）能够抑制活化的人外周血单个核细胞（PBMCs）释放粒细胞巨噬细胞集落刺激因子（GM-CSF）。由于白细胞介素（IL-4）和IL-13已被证明可抑制PBMCs释放细胞因子，我们测试了以下假设：前列环素与IL-4或IL-13联合使用可协同调节通常具有抗炎特性的IL-10以及促炎细胞因子肿瘤坏死因子α（TNF-α）的释放。为此，通过Ficoll分离PBMCs，用脂多糖（LPS）刺激，并在西卡前列素、IL-4或IL-13存在的情况下孵育。在用IL-4或IL-13孵育后，LPS刺激的PBMCs中TNF-α以及IL-10的分泌显著减少。相比之下，西卡前列素减少了TNF-α的分泌，但导致PBMCs释放的IL-10略有增加。当LPS激活的PBMCs在西卡前列素和IL-4或IL-13存在的情况下孵育时，对TNF-α的释放有选择性的协同抑制作用，而对IL-10则未观察到这种作用。因此，我们的数据表明前列环素可与细胞因子协同作用，选择性抑制PBMCs释放促炎细胞因子。
