The effect of heavy metals on the immune system at low concentrations.

The present study describes the effect of cadmium on lymphokines that cannot be directly traced to an allergen, or antigen in order to be able to explain various immunological processes. Exposure to various environmental pollutants is known to induce epithelial and inflammatory changes, characterized by a release of cytokines and other soluble mediators. Heavy metals like CdCl2 can induce, or inhibit the synthesis and expression of the inflammatory cytokines IL-1beta, IL-4, IL-6, TNF-alpha, IFN-gamma and ICAM-1. Normal human peripherial blood mononuclear cells (PBMCs) were exposed for different periods of times (1 to 96 h) to 0, 5, 25 and 50 micromoles CdCl2, and mRNA for the above cytokines was quantified by RT-PCR. Highly purified blood B cells and PBMCs from healthy donors were stimulated with IL-4 and aCD40 mAb and incubated with non-toxic concentrations of cadmium chloride (0,1-10 micromol). Levels of IgG and IgE were measured in the supernatants. Proliferation and expression of surface markers were determined by measuring [3H]-thymidine incorporation and by flow cytometry. The study showed that the in vitro synthesis of IgE by purified B cells or PBMCs stimulated with IL-4/aCD40 is inhibited by Cd at doses as low as 0,1 microM. Cd was found to inhibit IL-4/aCD40 induced proliferation of purified B cells and PBMCs in a dose dependent fashion. Most strikingly, only IgE but not IgG synthesis of purified B cells was inhibited by Cd. These data suggest that inhibition of IgE synthesis in human B lymphocytes by Cd seems to be a selective effect on immunoglobulin synthesis.