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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Inflammatory effects of phthalates in neonatal neutrophils.

Authors: Vetrano, Anna M; Laskin, Debra L; Archer, Faith; Syed, Kirin; Gray, Joshua P; Laskin, Jeffrey D; Nwebube, Nkiru; Weinberger, Barry

Published In Pediatr Res, (2010 Aug)

Abstract: Hospitalized infants are exposed to numerous devices containing the plasticizer di-(2-ethylhexyl) phthalate. Urinary levels of the phthalate metabolite, mono-(2-ethylhexyl) phthalate (MEHP), are markedly elevated in premature infants. Phthalates inactivate peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a nuclear transcription factor that mediates the resolution of inflammation, a process impaired in neonates. We speculate that this increases their susceptibility to MEHP, and this was analyzed. MEHP inhibited neutrophil apoptosis; neonatal cells were more sensitive than adult cells. In neonatal, but not in adult neutrophils, MEHP also inhibited chemotaxis, stimulated oxidative metabolism, and up-regulated expression of NADPH oxidase-1. In both adult and neonatal neutrophils, MEHP stimulated IL-1beta and VEGF production, whereas IL-8 production was stimulated only in adult cells. In contrast, MEHP-inhibited production of MIP-1beta by adult cells, and Regulated on Activation Normal T Cell Expressed and Secreted (RANTES) by neonatal neutrophils. The effects of MEHP on apoptosis and oxidative metabolism in neonatal cells were reversed by the PPAR-gamma agonist, troglitazone. Whereas troglitazone had no effect on MEHP-induced alterations in inflammatory protein or chemokine production, constitutive IL-8 and MIP-1beta production was reduced in adult neutrophils, and RANTES and MIP-1beta in neonatal cells. These findings suggest that neonatal neutrophils are more sensitive to phthalate-mediated inhibition of PPAR-gamma, which may be related to decreased anti-inflammatory signaling.

PubMed ID: 20453712 Exiting the NIEHS site

MeSH Terms: Adult; Apoptosis/drug effects; Chemotaxis/drug effects; Diethylhexyl Phthalate/analogs & derivatives; Diethylhexyl Phthalate/metabolism; Diethylhexyl Phthalate/pharmacology; Humans; Hydrogen Peroxide/metabolism; Infant, Newborn; Inflammation/chemically induced*; Neutrophils*/drug effects; Neutrophils*/immunology; Oxidants/metabolism; PPAR gamma/metabolism; Phthalic Acids/pharmacology*; Plasticizers/metabolism; Plasticizers/pharmacology; Signal Transduction/drug effects

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