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BioMetals

, Volume 26, Issue 3, pp 369–385 | Cite as

Metallic gold beads in hyaluronic acid: a novel form of gold-based immunosuppression? Investigations of the immunosuppressive effects of metallic gold on cultured J774 macrophages and on neuronal gene expression in experimental autoimmune encephalomyelitis

  • Dan Sonne PedersenEmail author
  • Thao Phuong Tran
  • Kamille Smidt
  • Bo Martin Bibby
  • Jørgen Rungby
  • Agnete Larsen
Article

Abstract

Multiple sclerosis (MS) is a neurodegenerative disease caused by recurring attacks of neuroinflammation leading to neuronal death. Immune-suppressing gold salts are used for treating connective tissue diseases; however, side effects occur from systemic spread of gold ions. This is limited by exploiting macrophage-induced liberation of gold ions (dissolucytosis) from gold surfaces. Injecting gold beads in hyaluronic acid (HA) as a vehicle into the cavities of the brain can delay clinical signs of disease progression in the MS model, experimental autoimmune encephalitis (EAE). This study investigates the anti-inflammatory properties of metallic gold/HA on the gene expression of tumor necrosis factor (Tnf-α), Interleukin (Il)-, Il-6, Il-10, Colony-stimulating factor (Csf)-v2, Metallothionein (Mt)-1/2, Bcl-2 associated X protein (Bax) and B cell lymphoma (Bcl)-2 in cultured J774 macrophages and in rodents with early stages of EAE. Cells grew for 5 days on gold/HA or HA, then receiving 1,000 ng/mL lipopolysaccharide (LPS) as inflammatory challenge. In the EAE experiment, 12 Lewis rats received gold injections and control groups included 11 untreated and 12 HA-treated EAE rats and five healthy animals. The experiment terminated day 9 when the first ten animals showed signs of EAE, only one of which were gold-treated (1p = 0.0367). Gene expression in the macrophages showed a statistically significant decrease in Il-6, Il- and Il-10-response to LPS; interestingly HA induced a statistically significant increase of Il-10. In the EAE model gene expression of inflammatory cytokines increased markedly. Compared to EAE controls levels of Tnf-α, Il-, Il-10, Il-6, IL-2, Ifn-γ, Il-17, transforming growth factor (Tgf)-β, superoxide dismutase (Sod)-2, Mt-2 and fibroblast growth factor (Fgf)-2 were lower in the gold-treated group. HA-treated animals expressed similar or intermediate levels. Omnibus testing for reduced inflammatory response following gold-treatment was not significant, but tendencies towards a decrease in the Sod-2, Fgf-2, Il- response and a higher Bdnf and IL-23 gene expression were seen. In conclusion, our findings support that bio-liberation of gold from metallic gold surfaces have anti-inflammatory properties similar to classic gold compounds, warranting further studies into the pharmacological potential of this novel gold-treatment and the possible synergistic effects of hyaluronic acid.

Keywords

Anti-inflammation Dissolucytosis EAE Hyaluronic acid Macrophages Metallic gold 

Notes

Acknowledgments

The authors would like to thank Heidi Schou Knudsen and Karen Skjødt Sørensen for their excellent technical assistance and the animal department at The Department of Biomedicine for their help. We are grateful for financial support from the Aarhus University Research Foundation, Den Lægevidenskabelige Forskningsfond, Fonden af 17.12.1981 and Lykfeldts Legat.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Dan Sonne Pedersen
    • 1
    Email author
  • Thao Phuong Tran
    • 1
  • Kamille Smidt
    • 1
  • Bo Martin Bibby
    • 2
  • Jørgen Rungby
    • 1
  • Agnete Larsen
    • 1
  1. 1.Department of Biomedicine, PharmacologyAarhus UniversityAarhus CDenmark
  2. 2.Department of Public Health, Institute of BiostatisticsAarhus UniversityAarhus CDenmark

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