Patulin influences the expression of Th1/Th2 cytokines by activated peripheral blood mononuclear cells and T cells through depletion of intracellular glutathione

Patulin is a mold toxin secreted mainly by fungi of the Penicillium species. Exposure generally results from consumption of moldy fruits and fruit products. Since recent studies identified mold exposure as a risk factor for allergic diseases, we examined the effects of patulin on human peripheral blood mononuclear cells (PBMC) prepared from buffy coats of healthy donors. Cells were stimulated with CD3- and CD28-specific antibodies in the presence or absence of patulin. Effects of patulin on PBMCs were evaluated by proliferation, viability assays, and cytokine ELISAs. The presence of 50 ng/mL patulin strongly decreased the amounts of several cytokines in the supernatant of stimulated PBMCs. This decrease in cytokine secretion was not due to cytotoxic effects of patulin. Moreover, the extent of the reduction of cytokine amounts was cytokine specific, affecting some (IL-4, IL-13, IFNgamma, and IL-10), but not others (IL-8, IL-5). We show that all effects could be abolished by adding thiol containing compounds. A depletion of intracellular GSH could be measured after incubation of cells with patulin. Taken together, our data indicate that patulin modulates the functional activation of PBMCs with respect to proliferation and cytokine secretion patterns by depletion of intracellular GSH. The depletion of intracellular glutathione may influence the balance between Th1 and Th2 cells and have implications for allergic diseases.