TH1-directed modulation of in vitro cytokine production in human peripheral blood mononuclear cells by styrene-7.8-oxide

Styrene and its chiral main metabolite styrene-7.8-oxide are well characterized regarding their cytotoxic, genotoxic and neurotoxic properties. To our knowledge, no data exist on the influence of styrene and styrene-7.8-oxide on immune reactions. Epidemiological studies suggest that exposure to environmental pollutants, specifically volatile organic compounds (VOCs), including styrene is one factor contributing to increasing prevalence rates of allergic diseases. In this study, we investigated the modulation of the immune system by styrene-7.8-oxide in vitro. Human peripheral blood mononuclear cells were incubated with styrene-7.8-oxide, either as (S)-enantiomer, (R)-enantiomer, or racemic styrene-7.8-oxide. Subsequently, the secretion of TH1-cytokines IFNγ and IL-12 as well as TH2-cytokines IL-4 and IL-5 were measured by ELISA. We introduced a novel mathematical approach to quantify and compare cytokine responses. The results revealed a stimulation of cytokine secretion with emphasis on TH1-cytokines IFNγ and IL-12. The stimulating effects were elicited at concentrations of styrene-7.8-oxide comparable to what would be encountered at industrial workplaces where styrene is processed. Therefore, we conclude that styrene-7.8-oxide exhibits immunomodulating capacities, which can be of clinical relevance for individuals with high styrene exposure.