The in vitro immune modulation by cadmium depends on the way of cell activation

Among environmental contaminants known for their toxicity and worldwide distribution, heavy metals are of primary concern. Although the toxicology of cadmium (Cd) has been extensively studied, little information is available on the immunomodulation driven by exposure to low doses of Cd. We aimed to evaluate the immunomodulatory effects elicited by short-term exposure of human immunocompetent cells to low biologically relevant doses of Cd in two activation models. Human peripheral blood mononuclear cells, activated either by bacterial antigens (heat-killed Salmonella Enteritidis) or monoclonal antibodies (mAb: anti-CD3/anti-CD28/anti-CD40), were exposed to Cd acetate for 24h. Cell vitality was determined by MTT assay, cytokine release by ELISA, and cytokine gene expression by real-time RT-PCR. The results demonstrated that, in addition to the known toxic effects of Cd, doses from 0.013 to 13.3 microM exert differential effects on cytokine production. In the case of mAb-activation, secretion of interleukin (IL)-1 beta, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma was greatly inhibited at low Cd doses compared to production of IL-4 and IL-10. This indicates a type-2-biased immune response. Under stimulation by bacterial antigens, release of IL-10 was highly suppressed compared to that of IFN-gamma and TNF-alpha; IL-4 was undetectable. These results imply that low Cd doses exert immunomodulatory effects and the direction of this modulation depends on the pathway to cell activation. Overall, Cd polarizes the immune response toward type-2 in cells stimulated via T cell receptors. However, a polarized type-1 response induced by bacterial antigens could not be overwhelmed by the effects of Cd.