Toxicological Sciences 66, 117-124 (2002)
Copyright © 2002 by the Society of Toxicology
IMMUNOTOXICOLOGY |
Effect of a Single Oral Dose of 2,3,7,8-Tetrachlorodibenzo-p-dioxin on Immune Function in Male NC/Nga Mice
,1
* National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan;
CREST Japan Science and Technology Corporation, Kawaguchi, Saitama, Japan; and
National Institute of Radiological Sciences, Inage, Chiba, Japan
Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces immunosuppression in humans and animals. However, the effect of TCDD on Th2-type immune responses such as allergic reactions has been unclear. Using NC/Nga mice that developed atopic dermatitis-like skin lesions with marked elevation in plasma of total IgE when bred under conventional conditions, we investigated the effects of a single oral dose of TCDD on immune responses. NC/Nga mice received a single oral dose (0 or 20 µg/kg body weight) of TCDD. On day 7, treatment with TCDD alone decreased the cellularity of thymus. However, treatment with TCDD modified the cellularity of spleens and mesenteric lymph nodes (MLNs) but not of the thymus on day 28. When NC/Nga mice received ip immunization with OVA and alum on the same day as the TCDD treatment (0, 5, or 20 µg/kg body weight), TCDD markedly suppressed the concentrations of Th2-type cytokines (e.g., IL-4 and IL-5) in culture supernatants of spleen cells, whereas IFN-
production significantly increased. TCDD exposure reduced anti-OVA and total IgE antibody titers in plasma and did not induce the development of atopic dermatitis-like lesions in the pinnae or dorsal skin of NC/Nga mice. These results suggest that in NC/Nga mice, exposure to TCDD may impair the induction of Th2-type immune responses.
Key Words: allergy; NC/Nga; TCDD; Th1/Th2; immunosuppression; cytokine.
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