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Published on: January 7, 2019

Aspects of dioxin toxicity are mediated by interleukin 1-like cytokines

Kalyan Pande1, Susan M Moran, Christopher A Bradfield

  • 1McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison, 53706-1599, USA.

Molecular Pharmacology
|February 22, 2005
PubMed

Insights

Interleukin 1 (IL1)-like cytokines partially mediate 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) toxicity. Mice lacking IL1 receptors showed reduced liver damage and inflammation after dioxin exposure.

Area of Science:

  • Toxicology
  • Immunology
  • Molecular Biology

Background:

  • 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) induces a wide range of toxic effects.
  • Dioxin's toxicity is primarily mediated by its binding to the aryl hydrocarbon receptor.
  • Interleukin 1 (IL1)-like cytokines are implicated in chemically induced toxicity.

Purpose of the Study:

  • To investigate the role of IL1-like cytokines in the acute toxic responses to dioxin.
  • To determine if IL1 signaling pathways contribute to dioxin-induced liver damage and inflammation.

Main Methods:

  • Utilized a "triple-null" mouse model lacking receptors for tumor necrosis factors (TNFs) and IL1 cytokines.
  • Administered dioxin to triple-null mice and control groups.
  • Assessed serum alanine aminotransferase levels, liver inflammation, thymic involution, Cyp1a2 induction, hepatomegaly, and hydropic degeneration.

Main Results:

  • Triple-null mice exhibited significantly reduced serum alanine aminotransferase levels, indicating attenuated hepatocellular damage.
  • Protection from dioxin-induced liver inflammation was observed in the triple-null mice.
  • Thymic involution, Cyp1a2 induction, hepatomegaly, and hydropic degeneration were not affected by the absence of IL1 receptors.

Conclusions:

  • IL1-like cytokines play a significant role in mediating dioxin-induced liver injury and inflammation.
  • Targeting IL1 signaling pathways may offer a therapeutic strategy for mitigating certain dioxin toxicities.
  • The aryl hydrocarbon receptor pathway is not solely responsible for all dioxin-induced toxic effects.

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