Influence of Phthalates on in vitro Innate and Adaptive Immune Responses

TY - JOUR

T1 - Influence of Phthalates on in vitro Innate and Adaptive Immune Responses

AU - Hansen, Juliana Frohnert

AU - Nielsen, Claus Henrik

AU - Brorson, Marianne Møller

AU - Frederiksen, Hanne

AU - Hartoft-Nielsen, Marie-Louise

AU - Rasmussen, Åse Krogh

AU - Bendtzen, Klaus

AU - Feldt-Rasmussen, Ulla

PY - 2015/6/25

Y1 - 2015/6/25

N2 - Phthalates are a group of endocrine disrupting chemicals, suspected to influence the immune system. The aim of this study was to investigate the influence of phthalates on cytokine secretion from human peripheral blood mononuclear cells. Escherichia coli lipopolysaccharide and phytohemagglutinin-P were used for stimulation of monocytes/macrophages and T cells, respectively. Cells were exposed for 20 to 22 hours to either diethyl, di-n-butyl or mono-n-butyl phthalate at two different concentrations. Both diesters were metabolised to their respective monoester and influenced cytokine secretion from both monocytes/macrophages and T cells in a similar pattern: the secretion of interleukin (IL)-6, IL-10 and the chemokine CXCL8 by monocytes/macrophages was enhanced, while tumour necrosis factor (TNF)-α secretion by monocytes/macrophages was impaired, as was the secretion of IL-2 and IL-4, TNF-α and interferon-β by T cells. The investigated phthalate monoester also influenced cytokine secretion from monocytes/macrophages similar to that of the diesters. In T cells, however, the effect of the monoester was different compared to the diesters. The influence of the phthalates on the cytokine secretion did not seem to be a result of cell death. Thus, results indicate that both human innate and adaptive immunity is influenced in vitro by phthalates, and that phthalates therefore may affect cell differentiation and regenerative and inflammatory processes in vivo.

AB - Phthalates are a group of endocrine disrupting chemicals, suspected to influence the immune system. The aim of this study was to investigate the influence of phthalates on cytokine secretion from human peripheral blood mononuclear cells. Escherichia coli lipopolysaccharide and phytohemagglutinin-P were used for stimulation of monocytes/macrophages and T cells, respectively. Cells were exposed for 20 to 22 hours to either diethyl, di-n-butyl or mono-n-butyl phthalate at two different concentrations. Both diesters were metabolised to their respective monoester and influenced cytokine secretion from both monocytes/macrophages and T cells in a similar pattern: the secretion of interleukin (IL)-6, IL-10 and the chemokine CXCL8 by monocytes/macrophages was enhanced, while tumour necrosis factor (TNF)-α secretion by monocytes/macrophages was impaired, as was the secretion of IL-2 and IL-4, TNF-α and interferon-β by T cells. The investigated phthalate monoester also influenced cytokine secretion from monocytes/macrophages similar to that of the diesters. In T cells, however, the effect of the monoester was different compared to the diesters. The influence of the phthalates on the cytokine secretion did not seem to be a result of cell death. Thus, results indicate that both human innate and adaptive immunity is influenced in vitro by phthalates, and that phthalates therefore may affect cell differentiation and regenerative and inflammatory processes in vivo.

KW - Adaptive Immunity

KW - Cytokines

KW - Dibutyl Phthalate

KW - Female

KW - Humans

KW - Immunity, Innate

KW - Lipopolysaccharides

KW - Macrophages

KW - Male

KW - Monocytes

KW - Phthalic Acids

KW - Phytohemagglutinins

KW - T-Lymphocytes

U2 - 10.1371/journal.pone.0131168

DO - 10.1371/journal.pone.0131168

M3 - Journal article

C2 - 26110840

SN - 1932-6203

VL - 10

JO - P L o S One

JF - P L o S One

IS - 6

M1 - e0131168

ER -