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

Juliana Frohnert Hansen,Claus Henrik Nielsen,Ulla Feldt-Rasmussen,Klaus Bendtzen,Åse Krogh Rasmussen,Marianne Møller Brorson,Marie-Louise Hartoft-Nielsen,Hanne Frederiksen,Wenyu Lin

doi:10.1371/journal.pone.0131168

Juliana Frohnert Hansen, Claus Henrik Nielsen + Show 7 more

Open Access

https://doi.org/10.1371/journal.pone.0131168

Copy DOI

Journal: PloS one	Publication Date: Jun 25, 2015
Citations: 41	License type: CC BY 4.0

Affiliation: Rigshospitalet, University of Copenhagen

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.

Highlights

Phthalates are a group of endocrine disrupting chemicals (EDCs), with hundreds of million tons produced each year [1]
Both di-ethyl phthalate (DEP) and Di-n-butyl phthalate (DnBP) were metabolised in mononuclear cells (MNC) to their respective monoesters (MEP and mono-n-butyl phthalate (MnBP)), and all of the added MnBP was recovered as the monoester (n = one cell culture, unstimulated, in single determination, data not shown), demonstrating no further metabolism
Hundred μM of DEP was metabolised to 120 μM of MEP (n = one well in single determination), but 100 μM of DnBP was metabolised to 61 μM MnBP (n = one well in single determination)

Summary

Introduction

Phthalates are a group of endocrine disrupting chemicals (EDCs), with hundreds of million tons produced each year [1]. Phthalates added during the manufacturing process are not chemically bound to the end-products and leach into the environment. Exposure to humans and wildlife cannot be avoided due to their ubiquitous presence [2,3,4]. Phthalates are produced by the industry as lipophilic diesters, which are rapidly metabolised to their respective monoester. Large phthalate molecules are further metabolised to oxidative metabolites [5,6].

Objectives

Methods

Results

Discussion

Conclusion