title: Immunostimulatory capacity of dental casting alloys on endotoxin responsiveness.
abstract: BACKGROUND
  Oral metal exposure has been associated with systemic and local adverse reactions, probably due to elemental release from the alloys. Although supraphysiological concentrations of salts from dentally applied metals can activate innate cells through TLR4 (Ni, Co, Pd) and TLR3 (Au), whether direct exposure to solid alloys can also trigger innate immune reactivity is still unknown.
  
  
  OBJECTIVE
  The purpose of this in vitro study was to determine whether dental cast alloy specimens can activate innate cells and influence their responsiveness to bacterial endotoxin.
  
  
  METHODS
  Human monocyte-derived dendritic cells (MoDC) and THP-1 cells were cultured on top of different alloy specimens (Ni-Cr, Co-Cr, Pd-Cu, Pd-Ag, Ti-6Al-4V, amalgam, gold, and stainless steel) or in alloy-exposed culture medium with or without endotoxin (lipopolysaccharide [LPS]; Escherichia coli 055:B5). Interleukin-8 (IL-8) production was used as the parameter for innate stimulation and evaluated by enzyme-linked immunosorbent assay after 24 hours of culture. The statistical significance of the effects of various casting alloys on the secretion of IL-8 was analyzed by using the nonparametric Wilcoxon rank sum test (α=.05).
  
  
  RESULTS
  Dental cast alloys induced IL-8 production in MoDC and THP-1 cells, with Au and Pd-Cu providing the strongest stimulation. The alloy-exposed culture media tested contained sufficient stimulatory metal ions to induce detectable IL-8 production in THP-1 cells, except for the Ni-Cr and stainless steel exposed media. Au and Pd-Cu alloys were also most effective in potentiating LPS responsiveness as measured by IL-8 production.
  
  
  CONCLUSIONS
  Using an in vitro culture system to expose MoDC and THP-1 cells to different alloy specimens this study showed that contact with the solid alloys, in particular when they contain Pd or Au, can trigger innate immune responses and augment responsiveness to bacterial endotoxin.
authors.affiliation: Postgraduate student, Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands; and Lecturer, Department of Biomedical Science, Faculty of Dentistry, University of Jember, Jember, Indonesia. Electronic address: d.rachmawati@unej.ac.id.
authors.forename: Dessy
authors.initials: D
authors.lastname: Rachmawati
authors.affiliation: Medical Immunologist, Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: B Mary E
authors.initials: BME
authors.lastname: von Blomberg
authors.affiliation: Professor, Department of Dental Materials Science, Academic Center for Dentistry Amsterdam, VU University Amsterdam and University of Amsterdam, The Netherlands.
authors.forename: Cornelis J
authors.initials: CJ
authors.lastname: Kleverlaan
authors.affiliation: Professor, Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Rik J
authors.initials: RJ
authors.lastname: Scheper
authors.affiliation: Associate Professor, Medical Immunologist, Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Ingrid M W
authors.initials: IMW
authors.lastname: van Hoogstraten
mesh_terms: D003035:Cobalt / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D003722:Dental Alloys; D003735:Dental Casting Technique; D004731:Endotoxins / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006046:Gold / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000276:immunology; D008422:Materials Testing; D009532:Nickel / Q000276:immunology; D010165:Palladium / Q000276:immunology; D018709:Statistics, Nonparametric
chemical_list: D003722:Dental Alloys; D004731:Endotoxins; D016209:Interleukin-8; D003035:Cobalt; D010165:Palladium; D006046:Gold; D009532:Nickel