Reassessing the Efficacy of Gold Therapy for Rheumatoid Arthritis

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A combination of oral methotrexate and intramuscular gold therapy is effective on RA-related symptoms.
A combination of oral methotrexate and intramuscular gold therapy is effective on RA-related symptoms.

Because of its purity, gold is an inert element when used in the human body. This biocompatibility has made it extremely useful in many areas of dentistry and medicine. Its anti-inflammatory and antimicrobial actions have since been widely recognized.

The mechanisms whereby gold compounds exert anti-inflammatory effects are not fully understood, but mounting evidence indicates that gold is stored in lysosomes in which it inhibits the processing of antigenic agents and the release of inflammatory cytokines.1,2 

Studies initially investigating the use of gold in rheumatoid arthritis, showed potential uses of the metal in antimicrobial and antiviral therapies. Ongoing studies exploring the use of gold in the treatment of conditions such as cancer and human immunodeficiency virus show promising potential.

Even though the use of gold products to treat rheumatoid arthritis has declined since the development of newer anti-inflammatory agents and biologic disease-modifying antirheumatic drugs (DMARDs), its efficacy still appeals to many. 

In a systematic review of auranofin for the treatment of rheumatoid arthritis, this gold compound was found to be more efficacious than placebo in relieving tender joints, pain, and reducing erythrocyte sedimentation rate.3

In a 48-week randomized, placebo-controlled trial, researchers examined the effects of a combination of oral methotrexate and intramuscular gold therapy in patients with rheumatoid arthritis whose disease was not sufficiently controlled by methotrexate alone. Significant clinical improvement was reported after adding intramuscular gold therapy to methotrexate.4

The same mechanisms of action are being explored for possible anticancer and antimicrobial properties. Gold microparticles in a cancer cell appear to accelerate cell death and to upregulate tumor-suppressing signals.5 Gold has also been shown to inhibit growth of certain infectious microbes and to increase their susceptibility to oxidative stress and death.6 

Relatively low intracellular concentrations of gold microparticles are sufficient to inhibit growth of methicillin-resistant Staphylococcus aureus.7

Significant side effects associated with the long-term use of parenteral gold products have been observed, and include nephropathy, lung damage, and liver injury.8

The reassessment of an old therapy is not new in medicine, and the future of gold therapy looks bright. Increasing bacterial resistance to antibiotics has added energy to medical science's ever-expanding search for antibacterial and antiviral therapies. In addition, the use of gold therapy as an anticancer agent appears promising, as does its more common use as a DMARD.

References

  1. Seifert O, Matussek A, Sjögren F, Geffers R, Anderson CD. Gene expression profiling of macrophages: implications for an immunosuppressive effect of dissolucytotic gold ions. J Inflamm (Lond). 2012;9(1):43.
  2. Rigobello MP, Folda A, Baldoin MC, Scutari G, Bindoli A. Effect of auranofin on the mitochondrial generation of hydrogen peroxide: role of thioredoxin reductase. Free Radic Res. 2005;39(7):687-695.
  3. Suarez-Almazor ME, Spooner CH, Belseck E, Shea B. Auranofin versus placebo in rheumatoid arthritis. Cochrane Database Syst Rev. 2000;(2):CD002048.
  4. Lehman AJ, Esdaile JM, Klinkhoff AV, Grant E, Fitzgerald A, Canvin J. A 48-week, randomized, double-blind, double-observer, placebo-controlled multicenter trial of combination methotrexate and intramuscular gold therapy in rheumatoid arthritis: results of the METGO study. Arthritis Rheum. 2005;52(5):1360-1370.
  5. Park SH, Lee JH, Berek JS, Hu MC. Auranofin displays anticancer activity against ovarian cancer cells through FOXO3 activation independent of p53. Int J Oncol. 2014;45(4):1691-1698.
  6. Harbut MB, Vilchèze C, Luo X, et al. Auranofin exerts broad-spectrum bactericidal activities by targeting thiol-redox homeostasis. Proceedings Natl Acad Sci U.S.A. 2015;112(14):4453-4458.
  7. Hokai Y, Jurkowicz B, Fernández-Gallardo J, et al. Auranofin and related heterometallic gold(I)–thiolates as potent inhibitors of methicillin-resistant Staphylococcus aureus bacterial strains. J Inorg Biochem. 2014;138:81-88.
  8. Klinkhoff A. Major side effects of gold therapy. UpToDate. http://www.uptodate.com/contents/major-side-effects-of-gold-therapy. Updated March 22, 2016. Accessed July 14, 2016.
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