Scientists Probe Sepsis' Deadly Secrets

FRIDAY Aug. 17, 2007 -- Even when they appear clinically similar, patients with potentially deadly sepsis may be having different kinds of immune responses, say U.S. researchers who conducted the first large-scale natural history study of the common condition.

Sepsis -- a result of the body's inflammatory response to infection -- can lead to organ failure and death. Almost one million people in the United States will develop sepsis this year, and about 30 percent will die, making it the 10th leading cause of death in the country.

The University of Pittsburgh team said its findings suggest that past interpretations of how the immune system responds to infection were incorrect, because they were based on data from small studies. As a result, most of the treatments based on those studies have proven ineffective.

For this study, the University of Pittsburgh team evaluated data from almost 1,900 patients hospitalized with community-acquired pneumonia (CAP), the leading cause of severe sepsis. More than 30 percent of the patients developed severe sepsis, and 26 percent of those patients died.

The researchers found that 82 percent of the CAP patients had elevated cytokine levels, which were highest among those with fatal severe sepsis and lowest among those with no sepsis. Cytokines are signaling proteins especially involved in immune and inflammatory processes.

The study was published this week in the journal Archives of Internal Medicine.

"Our data show that much of what we previously thought about the role of the inflammatory response plays in sepsis was wrong or incomplete," Dr. John A. Kellum, professor in the department of critical care at the University of Pittsburgh School of Medicine, said in a prepared statement.

"We had thought the inflammatory response to infection was relatively short-lived, just a few days, and that it was similar in patients with similar clinical signs. Instead, we found that the inflammatory response was extremely variable across patients -- more than 50-fold differences were seen in some markers. Additionally, we found that the inflammatory response extends past the outward symptoms, far longer than previous data would suggest, and far longer than the courses of therapies used in unsuccessful clinical trials of experimental agents," Kellum said.

"We also found that the difference between the inflammatory response in a patient with a good outcome and a patient with a bad outcome is only a matter of degree."

Kellum and his colleagues said their findings indicate that treatments that completely abolish a specific component of the inflammatory response would be ineffective, and possibly even dangerous, because the inflammatory response is needed to deal with a patient's underlying infection.

Instead, better results might be achieved using therapies that tackle the chronic inflammatory response after sepsis and therapies that address multiple components.

More information

The MedlinePlus Medical Encyclopedia has more about sepsis.

Posted: August 2007


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