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Thimerosal induces TH2 responses via influencing cytokine secretion by human dendritic cells
Author(s) -
Agrawal Anshu,
Kaushal Poonam,
Agrawal Sudhanshu,
Gollapudi Sastry,
Gupta Sudhir
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0706467
Subject(s) - thimerosal , secretion , proinflammatory cytokine , dendritic cell , cytokine , biology , glutathione , intracellular , immunology , microbiology and biotechnology , endocrinology , biochemistry , immune system , inflammation , medicine , enzyme , dermatology
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‐α, 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‐γ) 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‐α, IL‐6, and IL‐12p70 by DC and IFN‐γ 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.