Study Suggests New Approach To Asthma

St. Louis, April 28, 1999 -- Although most scientists regard immune cells as the culprit in asthma, a new study suggests that resident airway cells may be at fault. These cells contain an anti-virus alarm system which, if not turned off, triggers persistent inflammation.

"I think this will change the way people think about asthma," says Michael J. Holtzman, M.D., head of the research team. "And it suggests therapeutic strategies that have not previously been considered."

Holtzman is the Selma and Herman Seldin Professor of Medicine, director of the Division of Pulmonary and Critical Care Medicine and associate professor of cell biology and physiology at Washington University School of Medicine in St. Louis. His team will report its findings in the May 1 issue of the Journal of Clinical Investigation (JCI). Lead author Deepak Sampath, Ph.D., was one of Holtzman's graduate students and now is a researcher with Wyeth-Ayerst.

Twenty years ago, Holtzman obtained the first evidence that the epithelial cells that line our airways may actively defend the body against infection. "Now it seems that these cells are in fact specially programmed for host defense and are abnormally programmed in people with asthma," he says.

He questions the traditional view that asthma is entirely an allergic response. In this scenario, an allergen such as dust or mold provokes immune cells to secrete chemicals -- cytokines -- that rally more immune cells to the site, triggering inflammation.

Holtzman notes that many asthmatic patients don't suffer from allergies and that most patients with allergies don't develop asthma. "That suggests some other contributing event," he says.

He has focused on one of the cellular signaling pathways that is controlled by molecules in the JAK/STAT family. This pathway responds to cytokines released during viral infection. When it is activated, a protein called Stat1 moves into the nucleus and switches on certain genes. The products o

Contact: Linda Sage
Washington University School of Medicine

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