Thimerosal induces TH2 responses via influencing cytokine secretion by human dendritic cells. J Leukoc Biol 81

Abstract: Thimerosal is an organic mercury com-pound 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 identi-fied. In this study, we investigated whether Thimer-osal can exercise a TH2-promoting effect through modulation of functions of dendritic cells (DC). Thimerosal, in a concentration-dependent man-ner, inhibited the secretion of LPS-induced proin-flammatory cytokines TNF-, 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-) cyto-kine 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-promot-ing effect of Thimerosal-treated DC, restoring se-cretion of TNF-, IL-6, and IL-12p70 by DC and IFN- secretion by T cells. These data suggest that modulation of TH2 responses by mercury and Thimerosal, in particular, is through depletion o