The adjuvant effect of di-(2-ethylhexyl) phthalate is mediated through a PPARalpha-independent mechanism

Toxicol Lett. 2007 May 15;170(3):223-8. doi: 10.1016/j.toxlet.2007.03.009. Epub 2007 Mar 20.

Abstract

Previous studies in BALB/c mice revealed an adjuvant effect of di-(2-ethylhexyl) phthalate (DEHP) to simultaneously administered ovalbumin. DEHP is the most commonly used phthalate plasticizer. In vivo formed metabolites of DEHP are peroxisome-proliferator-activated receptor (PPAR) ligands, a group of chemicals that may have immunomodulatory properties. To study whether the PPARalpha receptor was involved in the adjuvant effect of DEHP, PPARalpha-deficient 129/Sv mice were exposed intraperitoneally to a mixture of OVA and DEHP, and the OVA-specific IgE, IgG1 and IgG2a responses were compared to the corresponding responses in the wild-type strain. The study showed that the adjuvant mechanism of DEHP is mediated through a PPARalpha-independent mechanism. Compared to mice only given OVA, DEHP induced highly increased levels of OVA-specific IgG1 and IgG2a, both in the wild-type and in the PPARalpha knock-out strains, indicating that DEHP is a mixed Th1/Th2 adjuvant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic*
  • Animals
  • Diethylhexyl Phthalate / pharmacology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Immunization
  • Immunoglobulin E / biosynthesis
  • Immunoglobulin E / immunology
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin G / immunology
  • Mice
  • Mice, Knockout
  • Ovalbumin / immunology
  • PPAR alpha / genetics
  • PPAR alpha / physiology*
  • Reproducibility of Results
  • Th1 Cells / drug effects
  • Th1 Cells / immunology
  • Th2 Cells / drug effects
  • Th2 Cells / immunology

Substances

  • Adjuvants, Immunologic
  • Immunoglobulin G
  • PPAR alpha
  • Immunoglobulin E
  • Ovalbumin
  • Diethylhexyl Phthalate