Scientists Identify Substance in the Lung That May Be at the Heart of Life-Threatening Sepsis
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Scientists at The Feinstein Institute for Medical Research in Manhasset, NY, have discovered a substance in the lungs of patients in the throes of sepsis that travels to the heart and could trigger cardiac collapse, according to a new study presented at Sepsis 2007, an annual research meeting last week at the Institut Pasteur in Paris. Edmund J. Miller, PhD, director of cardiopulmonary research at The Feinstein, first identified the protein, macrophage migration inhibitory factor (MIF), being released by the lung in models of sepsis, a life-threatening immune system-mediated inflammatory response to a bacterial infection. Each year, 750,000 people in the United States develop severe sepsis and 215,000 will die no matter how hard doctors fight to save them. Scientists have spent decades trying to unravel this overwhelming response to an infection. The lungs are hard-hit in sepsis.
Dr. Miller is working with doctors in the medical intensive care at North Shore University Hospital in Manhasset, NY in a study of patients with severe sepsis. They are collecting blood during the first 12 hours of admission to the medical intensive care unit and then up to 120 hours later. As expected in these critically ill patients, 40 percent of the adult patients died from sepsis. They are also doing a similar study on a pediatric population at Schneider Children’s Hospital in New Hyde Park, NY.
While the MIF levels did not predict who would eventually die, the investigators did find that a large amount of the protein was coming from the lungs of those patients and traveling to the heart. They were able to take blood samples from patients before blood courses through the lung, and then after it leaves the lung and goes into the heart. It appears that those who died had increased levels of MIF in post-lung samples. By comparison, those who survived severe sepsis showed much smaller changes in the MIF levels from the venous blood sample to the arterial sample. In fact, there was a tendency for MIF levels to go down in the post-lung samples of those who didn’t succumb to the massive inflammatory response. “MIF has a profound effect on the heart,” explained Dr. Miller. “In severe sepsis, MIF is released from the lung into the heart, where it sends cardiac muscle cells into a spiraling death cycle.” Laboratory studies have shown that neutrophils, a white cell that is the first line of defense in an immune system attack on invading organisms, are summoned to the lung. When the neutrophil troops arrive to the scene, MIF levels increase. In the laboratory, MIF inhibitors developed by Yousef Al-Abed, PhD, of the The Feinstein Institute reduced the activity of MIF and prevented cardiac muscle cells from dying. Kaie Ojamaa, PhD, another scientist at The Feinstein, also collaborated on the study. “If the heart stops, then it is over,” said Dr. Miller. The scientists don’t know why MIF is produced in the lung during sepsis. They have shown that MIF levels, which are normally present in plasma in small amounts, goes up almost 200-fold during severe sepsis. Blocking MIF’s activity once it has been released from the lungs could save patients, Dr. Miller said. Many of the survivors also face life-long problems as a result of the assault on the body. Dr. Miller and his colleagues are trying to figure out how the body’s overwhelming inflammatory response injures the lungs. Severe sepsis can ultimately damage all the vital organs. MIF levels are also high in patients with acute respiratory distress syndrome. Dr. Miller has been studying acute lung injury since 1984. Six years into his research, in 1992, he discovered that interleukin 8 is a major neutrophil attractant in the lung. Today, inhibitors of interleukin 8 are in several stages of experimental testing in patients with lung damage. About The Feinstein Headquartered in Manhasset, NY, The Feinstein Institute for Medical Research is home to international scientific leaders in Parkinson's disease, Alzheimer’s disease, psychiatric disorders, rheumatoid arthritis, lupus, sepsis, inflammatory bowel disease, diabetes, human genetics, leukemia, lymphoma, neuroimmunology, and medicinal chemistry. The Feinstein Institute, part of the North Shore-LIJ Health System, ranks in the top 6th percentile of all National Institutes of Health grants awarded to research centers. Feinstein researchers are developing new drugs and drug targets, and producing results where science meets the patient. For more information, please visit www.FeinsteinInstitute.org or www.molmed.org. Media Contact: Jamie Talan 516-562-1232 |
