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Influence of phthalates on in vitro innate and adaptive immune responses.

Hansen JF, Nielsen CH, Brorson MM, Frederiksen H, Hartoft-Nielsen ML, Rasmussen ÅK, Bendtzen K, Feldt-Rasmussen U - PLoS ONE (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Endocrinology, PE 2132, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

ABSTRACT
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 di-ethyl, 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-γ 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.

No MeSH data available.


Related in: MedlinePlus

Influence of phthalates on the cytokine response of innate immune cells.MNC cultures were stimulated with 100 pg/ml E. coli LPS and exposed to di-ethyl phthalate (DEP), di-n-butyl phthalate (DnBP), or mono-n-butyl phthalate (MnBP), at two different concentrations, for 20–22 hours. The resulting production of IL-1β, IL-6, CXCL8, IL-10 and TNF-α are shown as ratio to the respective ethanol control. The red dashed line indicates the level of the ethanol controls (ratio = 1). * = p<0.05 compared to ethanol control, # = p<0.05 compared to low phthalate exposure (0.1 μM).
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pone.0131168.g001: Influence of phthalates on the cytokine response of innate immune cells.MNC cultures were stimulated with 100 pg/ml E. coli LPS and exposed to di-ethyl phthalate (DEP), di-n-butyl phthalate (DnBP), or mono-n-butyl phthalate (MnBP), at two different concentrations, for 20–22 hours. The resulting production of IL-1β, IL-6, CXCL8, IL-10 and TNF-α are shown as ratio to the respective ethanol control. The red dashed line indicates the level of the ethanol controls (ratio = 1). * = p<0.05 compared to ethanol control, # = p<0.05 compared to low phthalate exposure (0.1 μM).

Mentions: None of the investigated diesters nor the monoester were found to have any influence on IL-1β secretion by MNC. On the other hand, secretion of IL-6, CXCL8, IL-10 and TNF-α was significantly influenced by both diesters and by the monoester (Fig 1 and S1 Table). DEP and DnBP enhanced secretion of IL-6, CXCL8 and IL-10, but inhibited TNF-α secretion. The monoester, MnBP, enhanced the secretion of all four cytokines.


Influence of phthalates on in vitro innate and adaptive immune responses.

Hansen JF, Nielsen CH, Brorson MM, Frederiksen H, Hartoft-Nielsen ML, Rasmussen ÅK, Bendtzen K, Feldt-Rasmussen U - PLoS ONE (2015)

Influence of phthalates on the cytokine response of innate immune cells.MNC cultures were stimulated with 100 pg/ml E. coli LPS and exposed to di-ethyl phthalate (DEP), di-n-butyl phthalate (DnBP), or mono-n-butyl phthalate (MnBP), at two different concentrations, for 20–22 hours. The resulting production of IL-1β, IL-6, CXCL8, IL-10 and TNF-α are shown as ratio to the respective ethanol control. The red dashed line indicates the level of the ethanol controls (ratio = 1). * = p<0.05 compared to ethanol control, # = p<0.05 compared to low phthalate exposure (0.1 μM).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4482536&req=5

pone.0131168.g001: Influence of phthalates on the cytokine response of innate immune cells.MNC cultures were stimulated with 100 pg/ml E. coli LPS and exposed to di-ethyl phthalate (DEP), di-n-butyl phthalate (DnBP), or mono-n-butyl phthalate (MnBP), at two different concentrations, for 20–22 hours. The resulting production of IL-1β, IL-6, CXCL8, IL-10 and TNF-α are shown as ratio to the respective ethanol control. The red dashed line indicates the level of the ethanol controls (ratio = 1). * = p<0.05 compared to ethanol control, # = p<0.05 compared to low phthalate exposure (0.1 μM).
Mentions: None of the investigated diesters nor the monoester were found to have any influence on IL-1β secretion by MNC. On the other hand, secretion of IL-6, CXCL8, IL-10 and TNF-α was significantly influenced by both diesters and by the monoester (Fig 1 and S1 Table). DEP and DnBP enhanced secretion of IL-6, CXCL8 and IL-10, but inhibited TNF-α secretion. The monoester, MnBP, enhanced the secretion of all four cytokines.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Endocrinology, PE 2132, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

ABSTRACT
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 di-ethyl, 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-γ 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.

No MeSH data available.


Related in: MedlinePlus