New Treatment for Difficult-to-Treat Inflammatory Disease
Hypereosinophilic syndrome (HES) is an occasional disorder in which eosinophils, a type of inflammation-causing white blood cell, increase to excessive levels in the blood. The cells accumulate throughout the body and unleash powerful chemicals that can damage many different organs, including the heart, nervous system, skin, kidneys and digestive tract. Grantees of the National Institute of Allergy and Infectious Diseases (NIAID) have now used an existing cancer drug to effectively treat the disease in many individuals.
Eosinophils are a key component of anti-parasite immune responses and also play a central role in allergies. During HES, however, the cells appear in large numbers even though an underlying cause for their production is not known. The disease mostly affects men. Steroids, hydroxyurea and alpha interferon have all been used to treat the disease, but often unsuccessfully. Even when those treatments do work, they often cause unwanted side effects.
In a letter appearing in this week's The Lancet, Gerald Gleich, M.D., and colleagues from the Mayo Clinic and Foundation in Rochester, Minn., describe how a drug used to treat a form of leukemia is remarkably successful at reducing eosinophil levels in people with HES. The drug, imatinib mesylate, reduced eosinophil levels to normal in four of five patients studied and completely eliminated their symptoms.
"It's a different world," says Dr. Gleich, who has since moved to the University of Utah. "The disease is gone as long as the patients continue to take their medication."
The only patient who did not respond to the drug had elevated levels of interleukin-5, or IL-5, a protein in the blood that helps promote the growth of eosinophils. It is therefore likely that the drug was unable to work because IL-5 was constantly triggering the cells to reproduce.
Imatinib mesylate inhibits several enzymes that help regulate a cell's growth and reproduction. Its ability to shut down certain cancerous cells explains its effectiveness against leukemia. The HES patients received a much lower dose than is used in cancer treatment, however, suggesting eosinophils may contain a similar enzyme that is much more sensitive to the drug.
The low dosage also means people with HES may be able to keep their disease under control with a simple, inexpensive regimen. "The disease may be kept under control with two pills a week, compared to the four pills a day used to treat myelogenous leukemia," explains Dr. Gleich.
The study, though small, offers promise to people affected by HES. By highlighting how IL-5 and a potentially unknown enzyme might regulate eosinophils, the study also hints at new avenues for research. Says Dr. Gleich, "There is a crying need for a larger study."
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Reference:
GJ Gleich et al. Treatment of the hypereosinophilic syndrome with imatinib mesylate. The Lancet 359:1577-8 (2002).
Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site athttp://www.niaid.nih.gov.
NIAID is a component of the National Institutes of Health (NIH), an agency of the U.S. Department of Health and Human Services. NIAID supports basic and applied research to prevent, diagnose and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID also supports research on transplantation and immune-related illnesses, including autoimmune disorders, asthma and allergies.
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