Go for the Gold

Duke scientists may have solved the mystery surrounding the healing properties of gold—a discovery they say could renew interest in gold salts as a treatment for rheumatoid arthritis and other inflammatory diseases.

Physicians first used injections of gold salts in the early 1900s to ease the pain and swelling associated with arthritis.

But treatment came at a high cost: The shots took months to take effect and had side effects including rashes, mouth sores, kidney damage, and, occasionally, problems with the bone marrow's ability to make new blood cells.

Recently, new treatments such as methotrexate and biologically engineered drugs have replaced gold as a preferred treatment, and gold salts, while remaining effective, are usually administered as a last resort.

But David Pisetsky, chief of the division of rheumatology and immunology in the department of medicine, argues that gold shouldn't be dismissed so quickly. Pisetsky has long been interested in a molecule, HMGB1, that provokes inflammation, the key process underlying the development of rheumatoid arthritis.

Inside the nucleus, HMGB1 is a key player in transcription, the process that converts genetic information in DNA to its RNA equivalent. But, Pisetsky says, when HMGB1 is released from the cell—either through normal processes or cell death—it becomes a stimulus to the immune system and enhances inflammation. The molecule is especially prevalent around the joints, where arthritis occurs.

Working with colleagues at the University of Pittsburgh and the Karolinska Institute in Sweden, Pisetsky stimulated mouse and human immune system cells to secrete HMGB1, then treated them with gold salts.

The researchers found that the gold blocked the release of HMGB1 from the nucleus. In theory, that should lessen the amount available to provoke the body's immune system, thereby weakening the inflammatory response. The findings were published in the January issue of the Journal of Leukocyte Biology.