title: Effects of dental amalgam and heavy metal cations on cytokine production by peripheral blood mononuclear cells in vitro.
abstract: The effects of dental amalgam on cytokine production by human peripheral blood mononuclear cells (PBMC) from healthy donors were analyzed. To induce cytokine production, PBMC were stimulated with lipopolysaccharide, phytohemagglutinin, or staphylococcal enterotoxin A and cultured for 48 h in the presence of either freshly prepared amalgam, aged amalgam, or amalgam-conditioned culture medium (ACCM). The concentrations of several cytokines were measured in PBMC supernatants by enzyme-amplified sensitivity immunoassays (EASIAs). Freshly prepared amalgam as well as ACCM induced a decrease in the production of interferon-gamma (IFN-gamma) and interleukin-10 (IL-10), and an increase in the concentrations of tumor necrosis factor-alpha (TNF-alpha). Both fresh amalgam and ACCM showed no effects on IL-2, IL-6, or granulocyte-macrophage colony-stimulating factor levels. Amalgam aged for 6 weeks did not affect the concentration of any of the above cytokines. To investigate which heavy metal cations released from amalgam caused the observed immunomodulatory effects, Cu2+, Hg2+, and Sn2+, which were detected in amalgam supernatants by inductively coupled plasma atomic spectrophotometry, were added as salts to the cultures. Cu2+ and Hg2+ induced a decrease in IFN-gamma and IL-10 levels, and Hg2+ an increase in TNF-alpha concentrations. Cytokine production was not significantly modulated by Sn2+. Under these experimental conditions, release of Ag+ into culture medium was not detectable. However, Ag+ markedly suppressed the production of IFN-gamma, IL-10, and TNF-alpha. In summary, our results show that fresh amalgam, but not amalgam aged for 6 weeks, causes changes in the cytokine pattern of PBMC in vitro, and that these effects are due to the release of Cu2+ and Hg2+.
authors.affiliation: Institute of General and Experimental Pathology, University of Vienna, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Schedle
authors.forename: X H
authors.initials: XH
authors.lastname: Rausch-Fan
authors.forename: P
authors.initials: P
authors.lastname: Samorapoompichit
authors.forename: A
authors.initials: A
authors.lastname: Franz
authors.forename: F
authors.initials: F
authors.lastname: Leutmezer
authors.forename: A
authors.initials: A
authors.lastname: Spittler
authors.forename: M
authors.initials: M
authors.lastname: Baghestanian
authors.forename: T
authors.initials: T
authors.lastname: Lucas
authors.forename: P
authors.initials: P
authors.lastname: Valent
authors.forename: R
authors.initials: R
authors.lastname: Slavicek
authors.forename: G
authors.initials: G
authors.lastname: Boltz-Nitulescu
mesh_terms: D002412:Cations; D016207:Cytokines / Q000096:biosynthesis*; D003723:Dental Amalgam / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D019216:Metals, Heavy / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D013054:Spectrophotometry, Atomic
chemical_list: D002412:Cations; D016207:Cytokines; D019216:Metals, Heavy; D003723:Dental Amalgam