title: Immunomodulatory effects of metal salts at sub-toxic concentrations.
abstract: Because different metals are used in complementary medicine for the treatment of diseases related to a dysfunction of the immune system, this study aimed at determining the immunomodulatory potential of Pb(NO3)2, AuCl3, Cu(NO3)2, HgCl2, AgNO3, SnCl2, AsCl3and SbCl3at sub-toxic concentrations and at assessing possible toxic side effects of low-concentrated metal preparations. The influence of the metal salts on primary human mononuclear cells was analyzed by measuring cell viability using the water-soluble tetrazolium salt assay, apoptosis and necrosis induction by annexin V/propidium iodide staining and proliferation by carboxyfluorescein diacetate succinimidyl ester staining and flow cytometry. Effects on T-cell activation were assessed with CD69 and CD25 expression using flow cytometry whereas CD83, CD86 and CD14 expression was measured to evaluate the influence on dendritic cell maturation. Alterations of interleukin-2 and interferon-γ secretion were detected by enzyme-linked immunosorbent assay and genotoxic effects were analyzed using the comet assay. At sub-toxic concentrations retardation of T-cell proliferation was caused by Pb(NO3)2, AuCl3and Cu(NO3)2and inhibitory effects on interleukin-2 secretion were measured after incubation with Pb(NO3)2, AuCl3, Cu(NO3)2, HgCl2and AsCl3.Cu(NO3)2had immunosuppressive activity at dosages within the serum reference range for copper. All other metal salts showed effects at dosages above upper serum limits of normal. Therefore, only low-concentrated copper preparations are promising to have immunomodulatory potential. Toxic side effects of metal preparations used in complementary medicine are improbable because upper limits of metals set in the drinking water ordinance are either not exceeded or the duration of their application is limited. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Center for Complementary Medicine, Institute for Environmental Health Sciences and Hospital Infection Control, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Steinborn
authors.affiliation: Center for Complementary Medicine, Institute for Environmental Health Sciences and Hospital Infection Control, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Diegel
authors.affiliation: Center for Complementary Medicine, Institute for Environmental Health Sciences and Hospital Infection Control, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
authors.forename: Manuel
authors.initials: M
authors.lastname: Garcia-Käufer
authors.affiliation: Center for Complementary Medicine, Institute for Environmental Health Sciences and Hospital Infection Control, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Gründemann
authors.affiliation: Center for Complementary Medicine, Institute for Environmental Health Sciences and Hospital Infection Control, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
authors.forename: Roman
authors.initials: R
authors.lastname: Huber
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D020552:Comet Assay; D000529:Complementary Therapies; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects*; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D008670:Metals / Q000633:toxicity*; D009000:Monocytes / Q000187:drug effects; D009336:Necrosis / Q000139:chemically induced / Q000473:pathology; D009504:Neutrophils / Q000187:drug effects; D012492:Salts; D013601:T-Lymphocytes / Q000187:drug effects
chemical_list: D016207:Cytokines; D008670:Metals; D012492:Salts; D007371:Interferon-gamma
keywords: anthroposophic medicine; cytokine secretion; cytotoxicity; immunomodulation; metal salts; proliferation