Dr. Kevin Tracey

The finely balanced actions of the immune system protect people against everything from viruses to parasitic worms to cancer. Yet, as research in the last 30 years has shown, the immune system can also be a menace. Overproduction of signaling proteins called cytokines can lead to harmful inflammatory responses ranging from chronic conditions like rheumatoid arthritis and inflammatory bowel disease to life-threatening crises such as septic shock.

“We wouldn’t be healthy if evolution hadn’t conferred on us the ability to restrain the potential damage from cytokines,” says Dr. Kevin Tracey, director of the Feinstein Institute for Medical Research and president of the North Shore-LIJ Graduate School of Molecular Medicine.

Tracey will discuss his work on mechanisms that curb the inflammatory response in this year’s DeWitt Stetten, Jr. Lecture, titled, “Physiology and Immunology of the Cholinergic Anti-inflammatory Pathway.” The talk, which is part of the NIH Director’s Wednesday Afternoon Lecture Series and is sponsored by NIGMS, will be held on Wednesday, Oct. 24, at 3 p.m. in Masur Auditorium, Bldg. 10.

“What my colleagues and I have been studying is that the nervous system can be an off switch to prevent cytokine damage,” says Tracey. “This caught us and everyone else by surprise.” Tracey and his coworkers discovered that the vagus nerve, which winds from the brain through the chest and abdomen to interact with many major organs, can check cytokine production and prevent immune-mediated damage to the body.

Tracey calls this circuitry the “inflammatory reflex.” Unlike signals that accumulate gradually through the bloodstream, the neurological reflex he has discovered can respond rapidly to restrain cytokine action and prevent shock. Tracey explains that the inflammatory reflex could be why treatments such as relaxation therapy, acupuncture and meditation— all activities that increase the activity of the vagus nerve—can work to counteract inflammation.

Tracey, who now devotes himself to immunology research, was a practicing neurosurgeon for 10 years. NIGMS director Dr. Jeremy Berg says Tracey “has shown great initiative in linking two complicated systems—the nervous system and the immune system.”

NIGMS program director Dr. Scott Somers commends the way Tracey has grounded his model with molecular evidence. “Any number of people in the past have put animals in stressful conditions and measured standard physiological outputs,” he notes. “Tracey went right to the mechanisms, right to the receptors.”

The firing vagus nerve is known to produce acetylcholine. Tracey showed that macrophages and other immune system cells respond to this signal with a specific type of acetylcholine receptor on their surfaces. “That he found nicotinic acetylcholine receptors on immune cells provides convincing support for the mechanism,” says Berg.

After extensive studies in animals, Tracey is starting clinical studies to see if increasing the activity of the vagus nerve in people can help control inflammation. In the future, he foresees that devices or drugs that stimulate the vagus nerve or interact with the signaling pathway could be used to treat inflammation.

A book Tracey has written for a general audience, Fatal Sequence: The Killer Within, recounts the hospital course of a former patient, a baby girl with severe sepsis, and connects her case to subsequent discoveries about septic shock. “The book reflects a real interest in—and gift for—communication,” says Berg. This gift extends into Tracey’s research presentations, adds Somers.

“To get to know patients leaves a mark on your brain and heart and soul, but it’s a gift to be able to work in a laboratory and discover new things,” says Tracey. “Doing research is impossible without a tremendous amount of support. It’s gratifying to work on problems supported by taxpayer dollars that can hopefully give something back to the public. This is a very special responsibility.”

Tracey has headed a laboratory at the Feinstein Institute for Medical Research and the North Shore University Hospital in Manhasset, N.Y., since 1992. He earned a B.S. in chemistry from Boston College in 1979 and an M.D. from Boston University in 1983. He completed his clinical training in neurosurgery at the New York Hospital-Cornell University Medical College in 1992.

His honors include election to the American Society for Clinical Investigation in 2001 and lectureships from the Karolinska Institute, Harvard University and Washington University in St. Louis, among others. Tracey is editor in chief of Molecular Medicine and advisory editor for the Journal of Experimental Medicine. He has authored more than 240 research papers in the fields of immunology and neuroscience. The Institute for Scientific Information named him one of the most highly cited researchers in immunology in 2005.

NIGMS has supported Tracey’s research since 1999.

For more information or for reasonable accommodation, call Gloria Hairston at (301) 594-6747.