Kevin Tracey, MD studies the immune system and diseases caused by inflammation. With his colleagues, he discovered that the brain coordinates the immune system by sending electrical signals through nerves. Much like it controls the heart and other organs, the brain controls the output of cells that comprise the immune system. This discovery has altered the way that people think about how the body protects itself from infection and injury, because previously most had not considered the immune system to be directly controlled by the brain.

One long standing question in immunology has been, "how does the body normally control the immune system to prevent it from damaging normal organs?" Surprisingly, the vagus nerve – a long, thin nerve that snakes from the brain down through the body – directly controls the body’s inflammatory response. It provides a natural brake on the immune system, which is necessary because unless tightly controlled, the products of  the immune system can damage normal organs, as well as invading pathogens. Although many investigators had studied the effects of the immune system on brain, Tracey found that signals from the brain held the key to understanding the immune system. This answer gave important insights into how it is possible to prevent damage from inflammation.

Using pacemaker-like devices, it is now possible to stimulate the vagus nerve to reduce the production of cytokines, molecules produced by the immune system during inflammation which damage normal organs. The brain utilizes a neural circuit, coined the “inflammatory reflex,” which is dependent upon the activity of a molecule released by the vagus nerve – acetylcholine. The molecular mechanism for how acetylcholine turns off inflammation is through the alpha7 nicotinic acetylcholine receptor subunit, which turns off cytokine release from monocytes and other immune cells. Dr. Tracey’s team is now involved in testing the effects of vagus nerve stimulation and of drugs that target alpha7 in preclinical studies that may someday be used to prevent inflammation in diseases as varied as arthritis, colitis, diabetes, and atherosclerosis.

Dr. Tracey, a Cornell University Medical Center and Rockefeller University trained neurosurgeon, has been studying the molecular basis of inflammation since the caring for one his first patients, an eleven month old girl named "Janice," fighting for her life on the burn unit at New York Hospital. As recounted in his book "Fatal Sequence," Tracey's inability to explain the Janice's complicated hospital course at that time pushed him onto the path of exploring the immune system, its capacity to cause tremendous damage, and the mechanisms that normally function to keep us healthy. His highly cited work has yielded a new understanding of how the immune system functions, as well as experimental therapies to block inflammation by either targeting newly discovered cytokines, including HMGB1, or by preventing their production.