University of North Dakota Faculty/Staff Newsletter

Researcher discovers potential off switch for deadly response to infection or traumatic injury

Sepsis is a life-threatening medical condition with a high mortality rate that results from a runaway response by the body to fend off a severe infection or to recover from a traumatic injury. Combatting sepsis costs hospital ICUs $17 billion a year.

A UND researcher and her team have demonstrated for the first time that a molecule involved in the human body’s initial response to an infection or trauma may be the key in preventing sepsis, a life-threatening medical condition with a high mortality rate that results from a runaway inflammatory response by the body to fend off a severe infection or to recover from a traumatic injury.

“The mortality rate is very, very high—20 percent to 50 percent of people admitted to an ICU with sepsis are at risk of dying,” said Jyotika Sharma, a microbial immunologist in the Department of Microbiology and Immunology at the School of Medicine and Health Sciences.

“Inflammation occurs rapidly following infection, injury, or other trauma, and normally resolves within 24 to 72 hours,” said David S. Bradley, chair and associate professor of the Department of Microbiology and Immunology at the SMHS. “However, unresolved inflammation can result in sepsis with tissue damage, organ failure, and ultimately death. The ‘off switch’ for inflammation is poorly understood.”

The onslaught of sepsis is frighteningly fast; it can progress from simple sepsis to severe sepsis to septic shock sometimes within hours. Blood vessels are particularly affected by the hyperinflammation that accompanies sepsis. Extensive blood clotting occurs in vessels as a result of the ongoing inflammation, which disrupts blood flow and thus oxygen supply to the organs. Patients suffer a fever or hypothermia, a rapid heart rate, rapid respiration, and multiple organ failure because vital tissues lack perfusion with oxygen as a result of low blood pressure.

In addition to the high toll in lives lost, combatting sepsis is a huge drain on hospital resources. “Half of the ICU resources in this country are spent on these patients,” Sharma said. “The annual expenditure is around $17 billion.”

Sharma is the lead author of a research paper that will appear online in May and in the September print issue of the “Journal of Leukocyte Biology.” The journal’s editors found Sharma’s findings significant enough to garner a separate editorial in the journal. Bibhuti B. Mishra, a research associate professor in the Department of Microbiology and Immunology; and Sharma’s graduate students Anthony L. Steichen and Brandilyn J. Binstock co-authored the paper. The research paper is titled "C-type lectin receptor Clec4d plays a protective role in resolution of Gram negative pneumonia."

“Sharma’s group has demonstrated, for the first time that a host molecule is involved in programing the rapid turnover of neutrophils, the predominant cell involved in early inflammation,” Bradley said. “Its significance is the reason the journal has featured her work in their Frontline Science Section as leading edge research."

Sharma’s work is supported by funding from the National Institutes of Health and the American Heart Association.

-- Denis MacLeod, assistant director, Office of Alumni and Community Relations, School of Medicine and Health Sciences, 777.2733, denis.macleod@med.und.edu.


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