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ToxSci Advance Access published online on November 9, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfj043
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© The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received August 8, 2005
Accepted October 25, 2005

Immunotoxiocology

The Paradoxical Effects of Lead in Interferon-Gamma Knockout BALB/c Mice

Donghong Gao 1, Jane Kasten-Jolly 1, and David A. Lawrence 1*

1 Wadsworth Center, New York State Department of Health, Albany, New York 12201

* To whom correspondence should be addressed.
David A. Lawrence, E-mail: lawrencd{at}wadsworth.org


  Abstract

It has been reported that lead (Pb) exposure enhances IL-4 and inhibits interferon-gamma (IFN{gamma}) production in wild-type (WT) BALB/c mice. Here, we examined Pb effects on immunity in IFN{gamma} knockout (KO) mice. Pb significantly enhanced serum IgG1 anti-KLH levels in WT mice compared to the controls; Pb also increased serum IgG2a anti-KLH levels, but the IgG1:IgG2a ratio was greater with Pb. In addition, total serum IgE levels, but not IgE anti-KLH levels, were increased. In the KO mice, the serum IgG1, IgG2a, IgE anti-KLH and total IgE levels were significantly lower than those of WT mice. Surprisingly, Pb significantly enhanced IgG1and IgG2a anti-KLH levels in the KO mice. However, for these mice, unlike the WT mice, Pb caused a greater percentage change in IgG2a than in IgG1 anti-KLH, indicating less skewing toward type-2 immunoglobulins. Pb also enhanced the DTH response in WT mice. Not surprisingly, very low DTH occurred in the KO mice; however, Pb induced a strong KLH-specific DTH response. The in vivo Pb exposure significantly increased in vitro production of IL-4, IL-5, and IL-10, but not IFN{gamma}, IL-2 and IL-12, by KLH-induced WT and KO spleen cells. In contrast to KLH, DNFB CHS was detected in all groups, and Pb did not affect this response, which suggests that Pb has less effects on CD8+ T cell-related responses. As previously reported, Pb enhances Th2 responses in WT mice; however, in the KO mice, Pb enhanced Th1-related anti-KLH production and a Th2-related DTH. The Pb enhancement of DTH in IFN{gamma}-deficient mice is likely due to promotion of type-2 cytokines and enhancement of MHC class II expression.


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