Mynster Kronborg Thit, Frohnert Hansen Juliana, Nielsen Claus Henrik, Ramhøj Louise, Frederiksen Marie, Vorkamp Katrin, Feldt-Rasmussen Ulla
Department of Medical Endocrinology, PE 2132, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Institute for Inflammation Research, section 7521, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
PLoS One. 2016 Apr 29;11(4):e0154621. doi: 10.1371/journal.pone.0154621. eCollection 2016.
Although production of polybrominated diphenyl ethers (PBDEs) is now banned, release from existing products will continue for many years. The PBDEs are assumed to be neurotoxic and toxic to endocrine organs at low concentrations. Their effect on the immune system has not been investigated thoroughly. We aimed to investigate the influence of DE-71 on cytokine production by peripheral blood mononuclear cells (PBMCs) stimulated with Escherichia Coli lipopolysaccharide (LPS) or phytohaemagglutinin-L (PHA-L).
PBMCs isolated from healthy donors were pre-incubated with DE-71 at various concentrations and subsequently incubated with the monocyte stimulator LPS, or the T-cell activator PHA-L. Interferon (IFN)-γ, interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, IL-17A, and IL-17F were quantified in the supernatants by Luminex kits.
At non-cytotoxic concentrations (0.01-10 μg/mL), DE-71 significantly enhanced secretion of IL-1β, IL-6, CXCL8, IL-10, and TNF-α (p<0.001-0.019; n = 6) from LPS-stimulated PBMCs. IFN-γ, TNF-α, IL-17A, and IL-17F (p = <0.001-0.043; n = 6) secretion were enhanced from PHA-L-stimulated PBMCs as well. Secretion of IL-1β, IL-2, IL-10, IL-8 and IL-6 was not significantly affected by DE-71.
We demonstrate an enhancing effect of DE-71 on cytokine production by normal human PBMCs stimulated with LPS or PHA-L ex vivo.
尽管多溴二苯醚（PBDEs）的生产现已被禁止，但现有产品中的多溴二苯醚仍会持续释放多年。多溴二苯醚被认为在低浓度下具有神经毒性和对内分泌器官的毒性。它们对免疫系统的影响尚未得到充分研究。我们旨在研究DE-71对用大肠杆菌脂多糖（LPS）或植物血凝素-L（PHA-L）刺激的外周血单个核细胞（PBMCs）细胞因子产生的影响。
从健康供体分离的PBMCs与不同浓度的DE-71预孵育，随后与单核细胞刺激剂LPS或T细胞激活剂PHA-L孵育。通过Luminex试剂盒对外周血单个核细胞培养上清液中的干扰素（IFN）-γ、白细胞介素（IL）-1β、IL-2、IL-4、IL-6、IL-8、IL-10、肿瘤坏死因子（TNF）-α、IL-17A和IL-17F进行定量分析。
在无细胞毒性浓度（0.01 - 10μg/mL）下，DE-71显著增强了LPS刺激的PBMCs中IL-1β、IL-6、CXCL8、IL-10和TNF-α的分泌（p<0.001 - 0.019；n = 6）。PHA-L刺激的PBMCs中IFN-γ、TNF-α、IL-17A和IL-17F的分泌（p = <0.001 - 0.043；n = 6）也有所增强。DE-71对IL-1β、IL-2、IL-10、IL-8和IL-6的分泌没有显著影响。
我们证明了DE-71对体外LPS或PHA-L刺激的正常人PBMCs细胞因子产生具有增强作用。
