A first-of-its-kind study by University of Pittsburgh School of Medicine researchers is providing clues to one of the country’s leading causes of death. Sepsis, a runaway inflammatory response to infection, will strike nearly 1 million Americans this year, and about 300,000 will die. Pitt researchers revealed Monday in the peer-reviewed journal Archives of Internal Medicine that attempts to treat it have failed because they were developed with a flawed understanding of the disease. “This particular study, following the natural history of the disease in a large population, has never been done before on this level and it showed that the disease is far more complicated than anybody hoped,” said Scott Somers, who oversees sepsis grants at the National Institute of General Medical Sciences, part of the National Institutes of Health. The 10th leading cause of death in the United States, sepsis — which is not contagious, but rather results from the immune system’s response to infection — kills by triggering excessive inflammation to fight infection, reducing oxygen in the body and ultimately leading to organ failure. Drug companies have developed medicines to treat components of the disease, but have largely failed. With a $6 million federal grant and $2 million from pharmaceutical giant GlaxoSmithKline, Pitt scientists gathered data from 2,320 people who visited 28 hospital emergency rooms nationwide. They zeroed in on 1,886 patients hospitalized with community-acquired pneumonia, meaning they contracted the lung disease outside of a hospital. More than 30 percent of them, or 583 people, developed severe sepsis, and 149, or 26 percent of the sepsis patients, died. The scientists tracked sepsis in patients by measuring the level of cytokine — proteins that play an important part in the immune system by helping cells communicate with one another — in their blood. “What we found is that the inflammatory response doesn’t resolve rapidly, as was thought,” said Dr. John Kellum, a professor in Pitt’s department of critical care medicine and lead author of the study. “Despite the fact that patients look OK, that their fever was gone, that they didn’t look like they had an infection any longer — still they had levels of inflammatory cytokine in their blood.” The study also found that people of similar ages with similar symptoms in similar health had very different responses to sepsis and various treatments, leading the researchers to suspect that some people might be genetically predisposed to the condition. The Pitt researchers are planning several more studies using the information gathered and expect other scientists to use their findings to develop treatments. “This is a good study,” said Dr. Mitchell Levy, a professor of medicine at Brown University who does research on sepsis but was not involved in the Pitt study. “The important aspect of this study is that it provides the basis for future investigations.”

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