Gold was used extensively until the early 1980's when it was supplanted by methotrexate as the disease-modifying anti-rheumatic drug (DMARD) of choice. (DMARDS are drugs that actually slow down the progression of rheumatoid arthritis (RA) as opposed to non-steroidal anti-inflammatory drugs that merely help with symptoms.) More recently, biologic treatments have also entered the arena and are capable of putting RA into remission.

Gold treatment, while often effective, also was associated with a host of problems. The shots took months to take effect and side effects included rashes, mouth sores, kidney damage, inflammation of the lung, and occasionally, damage to the bone marrow causing life-threatening reductions in the number of red and white blood cell counts and platelet counts.

Dr. David Pisetsky, chief of the division of rheumatology at Duke University School of Medicine, says " We rheumatologists have really never understood how gold works.” His hope is that once the mechanism of action is understood, then it might be possible to create new and better gold-like drugs to treat arthritis.

Pisetsky's interest in gold comes from his work with a particular molecule, HMBG1, which causes inflammation, the linchpin to the development of rheumatoid arthritis. He states, “HMBG1 is a molecule which has two functions; it behaves one way when it's inside the nucleus of a cell, and …another way when it's released from a cell.”

Inside the nucleus, HMGB1 acts as a messenger and is responsible for converting genetic information from DNA to RNA. But when HMGB1 is released from the cell, for whatever reason, it stimulates the immune system and promotes inflammation…

Pisetsky feels that if HMGB1 were kept within the nucleus, it would help reduce the inflammation associated with arthritis.

HMGB1 prodcution in the body is heterogenous- it is not produced in the same concentration in every tissue of the body. There is an unusually high amount of it present within joints where arthritis occurs.

The experiments went like this... researchers at the University of Pittsburgh, the Karolinska Institute in Sweden, and Duke stimulated mouse and human immune system cells to make HMGB1, then treated the cells with gold. They found that the gold blocked release of HMGB1 from the nucleus. Theoretically, that should lessen the amount of HMGB1 available to promote an inflammatory response.

Pisetsky feels that gold works by interfering with the action of interferon beta and nitric oxide. These two substances help control the release of HMGB1.

(The study will appear in the January, 2008 issue of the Journal of Leukocyte Biology, but will be available ahead of print on the journal's website. Co-authors of the study include lead investigators Weiwen Jiang, from Duke University, and Cecilia Zetterstrom, from the Karolinska Institute; Heidi Wahamaa, Therese Ostberg, Ann-Charlotte Aveberger, Hanna Schierback and Ufl Anderson from the Karolinska Institute; Helena Erlandersson Harris, senior co-author, from the Medicine and Rheumatology Unit of the Karolinksa University Hospital and Michael Lotze, from the University of Pittsburgh.)

This description about how gold may work is fascinating to an arthritis specialist who started practice in 1981. At that time we had hydroxychloroquine, gold, and d-penicillamine. None of these treatments was ideal and both gold and d-penicillamine were very toxic. Our treatment options have increased greatly and we are now able to get many patients with RA into remission. However, we still have a ways to go. Research into the mechanisms of disease will help us find better therapies in the future. It may be that some of the older therapies like gold- if we can develop drugs that have the good effects… without the bad, may be very useful.

For more information on gold treatment go to http://www.arthritis-treatment-and-relief.com/gold-treatment.html