T cell-derived IL-5 production is a sensitive target of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

Chemosphere. 2005 Aug;60(7):907-13. doi: 10.1016/j.chemosphere.2005.01.014.

Abstract

The immune system is one of the organs most vulnerable to the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Among the various immunotoxic effects of TCDD, the thymus involution and suppression of IgM antibody production are well known sensitive reactions of the thymocytes and B cells affected by TCDD. Recently, we reported that TCDD greatly inhibits the production of type-2 helper T (Th2) cell-derived cytokines, especially IL-5, by the splenocytes in mice immunized with ovalbumin (OVA). In the present study, we investigated the dose-dependency of these TCDD immunotoxic effects in OVA-immunized mice to identify the most sensitive target. Mice of two age groups, 6 weeks old and 3 weeks old, were dosed with 0.3, 1.0, or 3.0 microg TCDD/kg and immunized with OVA using alum as an adjuvant. Seven days later, the thymus weight, thymocyte population, antigen-specific IgM in the plasma, and IL-5 production by the splenocytes were examined. Among them, IL-5 production was significantly suppressed by all three doses of TCDD and reduced to about 30% by even a small dose of 0.3 microg TCDD/kg in both age groups. The thymus weight was significantly reduced by 1.0 microg or 3.0 microg TCDD/kg, but IgM production was not affected by up to 3.0 microg/kg of TCDD in both age groups. Taken together, the Th2 cell-derived IL-5 production was the most sensitive endpoint detecting TCDD toxicity among those examined. Our results also suggest that effector T cells are targets more vulnerable to TCDD toxicity than thymocytes or antibody-producing B cells in the OVA-immunized mice.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • Female
  • Immunoglobulin M / blood
  • Interleukin-5 / immunology*
  • Lactation
  • Mice
  • Mice, Inbred C57BL
  • Organ Size / drug effects
  • Ovalbumin / immunology
  • Polychlorinated Dibenzodioxins / toxicity*
  • Spleen / cytology
  • Spleen / drug effects*
  • Spleen / immunology
  • Thymus Gland / cytology
  • Thymus Gland / drug effects
  • Thymus Gland / pathology
  • Weaning

Substances

  • Immunoglobulin M
  • Interleukin-5
  • Polychlorinated Dibenzodioxins
  • Ovalbumin