Monophthalates promote IL-6 and IL-8 production in the human epithelial cell line A549

Toxicol In Vitro. 2004 Jun;18(3):265-9. doi: 10.1016/j.tiv.2003.09.008.


The dramatically increasing prevalence of allergic respiratory diseases may in part be due to the presence of certain immunotoxic xenobiotics in the environment. Recent studies have suggested that some plasticizers belonging to the phthalate family, and metabolites thereof, play a role in the development of allergic respiratory diseases. This is probably due to an adjuvant effect, which in some cases may be combined with an inflammatory process. The scope of the present study was to investigate the inflammatory potential of monophthalates, which are degradation products of phthalate plasticizers. The human epithelial cell line A549 was exposed to 15.6-2000 microg/ml, in two-fold dilutions, to either mono-n-butyl phthalate, monobenzyl phthalate, mono-n-octyl phthalate, mono-2-ethylhexyl phthalate, mono-iso-nonyl phthalate or mono-iso-decyl phthalate. Concentrations of the proinflammatory cytokines IL-6 and IL-8 were measured in the cell culture supernatant by ELISA. The study showed that some, but not all, monophthalates could induce a concentration-dependent increase in cytokine production, whereas, at higher concentrations, all phthalates suppressed cytokine production. Both the stimulatory and the suppressive properties were highly dependent on the length of the alkyl side chain of the monophthalate - a structure-activity relationship that is supported by recent observations in mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Diethylhexyl Phthalate / analogs & derivatives*
  • Diethylhexyl Phthalate / toxicity
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Humans
  • Interleukin-6 / biosynthesis*
  • Interleukin-8 / biosynthesis*
  • No-Observed-Adverse-Effect Level
  • Phthalic Acids / toxicity*
  • Plasticizers / toxicity*
  • Structure-Activity Relationship


  • Interleukin-6
  • Interleukin-8
  • Phthalic Acids
  • Plasticizers
  • monoisononylphthalate
  • mono-n-octyl phthalate
  • Diethylhexyl Phthalate
  • mono-(2-ethylhexyl)phthalate
  • monobutyl phthalate