Abstract:
: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.
journal_name
J Leukoc Bioljournal_title
Journal of leukocyte biologyauthors
Agrawal A,Kaushal P,Agrawal S,Gollapudi S,Gupta Sdoi
10.1189/jlb.0706467subject
Has Abstractpub_date
2007-02-01 00:00:00pages
474-82issue
2eissn
0741-5400issn
1938-3673pii
jlb.0706467journal_volume
81pub_type
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