Effects of the Commercial Flame Retardant Mixture DE-71 on Cytokine Production by Human Immune Cells

PLoS One. 2016 Apr 29;11(4):e0154621. doi: 10.1371/journal.pone.0154621. eCollection 2016.

Abstract

Introduction: 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).

Material and methods: 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.

Results: 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.

Conclusions: We demonstrate an enhancing effect of DE-71 on cytokine production by normal human PBMCs stimulated with LPS or PHA-L ex vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytokines / biosynthesis*
  • Female
  • Flame Retardants / toxicity*
  • Halogenated Diphenyl Ethers / toxicity*
  • Humans
  • In Vitro Techniques
  • L-Lactate Dehydrogenase / metabolism
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / enzymology
  • Leukocytes, Mononuclear / immunology*
  • Lipopolysaccharides / pharmacology
  • Male
  • Phytohemagglutinins / pharmacology

Substances

  • Cytokines
  • Flame Retardants
  • Halogenated Diphenyl Ethers
  • Lipopolysaccharides
  • Phytohemagglutinins
  • leukoagglutinins, plants
  • pentabromodiphenyl ether
  • L-Lactate Dehydrogenase

Grants and funding

Ulla Feldt-Rasmussen received funding as main supervisor on the scholarship project “Interaction between thyroid autoimmunity and endocrine disrupting chemicals” by the Novo Nordisk foundation (application number: 13495), reference number: F-22222-1 for Thit Mynster Kronborg’s salary. Ulla Feldt-Rasmussen further received funding for research salary, equipment and material from the local region’s (RegionH, R129-A4222) research fund, from Arvid Nilsson’s Fund, Novo Nordisk Foundation (application number 8005 and 14266) and Danish Council for Independent Research (0602-01959B). Thit Mynster Kronborg received funding from the Danish Foundation ”Musikforlæggernes Agnes og Knut Mørks fond”, which sponsored equipment and materials. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.