In vitro IL-1 beta and TNF-alpha release from THP-1 monocytes in response to metal ions.
OBJECTIVE
Previous studies have shown that biomaterials can activate macrophages to produce cytokines and promote an inflammatory response. Although the toxicity of many metal ions has been extensively investigated, little is known about the ability of these ions to alter cytokine release from macrophages. Yet the release of these ions from biomaterials has been well documented. Previous studies indicated that alterations in cytokine release might be expected because metal ions alter protein production in macrophages at sub-toxic concentrations. Thus, the hypothesis of this study was that metal ions can alter the secretion of cytokines from macrophages at sub-toxic concentrations.


METHODS
The release of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) from macrophages was investigated when the macrophages were exposed to metal ions, with or without lipopolysaccharide (LPS), a component of dental plaque. Human THP-1 macrophages were exposed to ions of Ag, Au, Cu, Hg, and Ni for 24 h. In half of the cultures, LPS was added for the last 4 h. The release of IL-1 beta and TNF-alpha into the medium was measured using enzyme-linked immunosorbent assays. ANOVA and Tukey multiple comparison intervals were used to compare the various experimental conditions.


RESULTS
None of the metal ions elevated the IL-1 beta or TNF-alpha levels after 24 h, but Ni ions significantly elevated the IL-1 beta and TNF-alpha levels after 72 h. With LPS added, Ag, Cu, and Ni significantly amplified the LPS-induced production of IL-1 beta but only Ni amplified the TNF-alpha response. These alterations in cytokine response occurred with metal ion concentrations which have been previously shown to be released from dental alloys in vitro and in vivo.


CONCLUSIONS
It appeared plausible that macrophage-cytokine mediated inflammatory responses may be altered by the presence of some metal ions in tissues, particularly Ni.
Wataha
J C
JC
Department of Oral Rehabilitation, Medical College of Georgia School of Dentistry, Augusta, USA. watahaj@mail.mcg.edu
Ratanasathien
S
S
Hanks
C T
CT
Sun
Z
Z
D000704:Analysis of Variance; D003300:Copper / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006046:Gold / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis*; D007477:Ions; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008628:Mercury / Q000494:pharmacology; D008670:Metals / Q000494:pharmacology*; D009532:Nickel / Q000494:pharmacology; D012834:Silver / Q000494:pharmacology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D007375:Interleukin-1; D007477:Ions; D008070:Lipopolysaccharides; D008670:Metals; D014409:Tumor Necrosis Factor-alpha; D012834:Silver; D006046:Gold; D003300:Copper; D009532:Nickel; D008628:Mercury