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Influence of dental amalgam and heavy metal cations on in vitro interleukin-1beta production by human peripheral blood mononuclear cells.

The influence of dental amalgam and heavy metal cations on interleukin-1beta (IL-1beta) expression by peripheral blood mononuclear cells from healthy donors was studied. A marked decrease in the production of IL-1beta was caused by freshly prepared amalgam or amalgam-conditioned culture medium, but not by amalgam aged for 6 weeks. When metal cations were added as salts, Cu(2+), Hg(2+), and Ag(+) at high concentrations (33.3 and 333.3 microM) were highly inhibitory. Among other heavy metal cations, Au(3+), Pt(4+), Ni(2+), Pd(2+), but not Ga(3+) or Sn(2+), inhibited IL-1beta production in a concentration-dependent manner. Flow cytometry studies indicated that Hg(2+) and Ag(+) strongly reduced the percentage of CD14(+) cells containing IL-1beta intracellularly. As shown by Northern blot analysis, Hg(2+) inhibited the level of IL-1beta-specific mRNA by 28% at 3.3 microM and completely at 33.3 microM. Only slight inhibitory effects were induced by Cu(2+) at 33.3 microM. Interestingly, Ag(+) at a concentration of 3.3 microM increased twofold the amount of IL-1beta-specific mRNA. Our data show that IL-1beta production is altered at protein and mRNA levels by components released from fresh amalgam and by other heavy metal cations, suggesting a role of these cations in changes in the cell phenotype and IL-1-mediated cell functions.