Journal of Leukocyte Biology Myeloid cells, immune suppression, tumor immunology
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Originally published online as doi:10.1189/jlb.0706467 on November 1, 2006

Published online before print November 1, 2006
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(Journal of Leukocyte Biology. 2007;81:474-482.)
© 2007 by Society for Leukocyte Biology

Thimerosal induces TH2 responses via influencing cytokine secretion by human dendritic cells

Anshu Agrawal1, Poonam Kaushal, Sudhanshu Agrawal, Sastry Gollapudi and Sudhir Gupta

Division of Basic and Clinical Immunology, University of California, Irvine, California, USA

1 Correspondence: Division of Basic and Clinical Immunology, Med. Sci I C-240, University of California, Irvine, CA 92697, USA. E-mail: aagrawal{at}uci.edu

Thimerosal is an organic mercury compound that is used as a preservative in vaccines and pharmaceutical products. Recent studies have shown a TH2-skewing effect of mercury, although the underlying mechanisms have not been identified. In this study, we investigated whether thimerosal can exercise a TH2-promoting effect through modulation of functions of dendritic cells (DC). Thimerosal, in a concentration-dependent manner, inhibited the secretion of LPS-induced proinflammatory cytokines TNF-{alpha}, IL-6, and IL-12p70 from human monocyte-derived DC. However, the secretion of IL-10 from DC was not affected. These thimerosal-exposed DC induced increased TH2 (IL-5 and IL-13) and decreased TH1 (IFN-{gamma}) cytokine secretion from the T cells in the absence of additional thimerosal added to the coculture. Thimerosal exposure of DC led to the depletion of intracellular glutathione (GSH), and addition of exogenous GSH to DC abolished the TH2-promoting effect of thimerosal-treated DC, restoring secretion of TNF-{alpha}, IL-6, and IL-12p70 by DC and IFN-{gamma} secretion by T cells. These data suggest that modulation of TH2 responses by mercury and thimerosal, in particular, is through depletion of GSH in DC.

Key Words: APC • heavy metal • immune modulation






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