Dual purpose: some cancer therapies used to treat autoimmune diseases.

In July 1917, when German forces first used mustard gas (sulfur mustard) as a chemical warfare agent against British troops in Ypres, Belgium, no one would have predicted that any good would come of it. The first hint came in 1919, when E.B. and H.D. Krumbhaar reported that victims of mustard gas poisoning had low white blood cell counts and atrophy of the bone marrow and lymphatic tissues. These observations and subsequent research on the closely related nitrogen mustards ultimately led to clinical studies in the early 1940s showing that the nitrogen mustard compound mechlorethamine had beneficial effects in patients with Hodgkin disease and other lymphomas. The introduction of mechlorethamine into clinical practice launched the modern era of cancer chemotherapy. Because of its immunosuppressive properties, nitrogen mustard was also one of the first cancer chemotherapy drugs used for treating other diseases— in particular, those that appeared to involve heightened or abnormal immune system activity. Whereas suppressing the immune system " is not desirable in treating cancer, it happens that the same action is beneficial for people with autoimmune disease, " said Bruce Chabner, M.D., clinical director of the Massachusetts General Hospital Cancer Center in Boston. Established Therapies The goal of chemotherapy in the treatment of autoimmune and inflam-matory disorders is to dampen the activity of the immune system rather than to kill abnormal cells. To achieve this goal and minimize side effects, the doses used are lower than those used in treating cancer. Among the most widely used drugs is methotrexate, an antimetabolite that interferes with various aspects of normal cellular metabolism. Methotrexate has become the standard therapy for moderate to severe rheumatoid arthritis. And, said Michael Weinblatt, M.D., co-director of clinical rheumatology at Boston's Brigham and Women's Hospital, rheumatologists often use methotrexate in combination with other drugs for treating rheumatoid arthritis—a concept that " was essentially lifted from the oncologists " and has proved to be successful. Methotrexate also plays a role in the management of numerous other autoimmune diseases, including psoriatic arthritis, polymyositis, Crohn disease, and certain types of vasculitis (blood vessel inflammation). It is also used for severe cases of psoriasis—a disorder marked by inflammation and abnormally rapid turnover of skin cells. Azathioprine (Imuran), an immunosup-pressive antimetabolite that is a derivative of the cancer drug 6-mercaptopu-rine, is also used to treat many autoim-mune and inflammatory diseases and was one of the first drugs used to prevent organ …