Modeling sepsis in newborns

September 6, 2012

Sepsis, or bacterial infection of the bloodstream, is a grave, hard-to-diagnose threat in premature newborns in the NICU. Even when it's detected and treated with antibiotics, its inflammatory effects can harm fragile babies' development. Now, researchers at Boston Children's Hospital have modeled the effects of sepsis on the unique newborn immune system, using mice. They and others have begun using the model to identify diagnostic markers and better treatments.

The new model is described September 6 in the online open-access journal .

Premature infants typically are kept alive with catheters and intravenous lines that are vital for their care, but that also carry a risk of , most commonly from the bacterium . can now avoid many of these infections, but those that slip through can be hard to spot and treat.

"When infection occurs, it's hard to detect in newborns, who can't speak and, due to their unique immune systems, tend not to have fevers or show clinical signs," explains Ofer Levy, MD, PhD, of the Division of Infectious Diseases at Boston Children's and senior author on the paper. "There may be irregular breathing or increased heart rate, or the baby may be acting a little 'off,' but these signs are pretty nonspecific. There's a tremendous need for better diagnostics in this field."

Mouse models of intravenous infections in newborns have been lacking, due to the technical challenge of working with tiny newborn mice. With great , Kenny Kronforst, MD, MPH, a clinical Newborn Medicine fellow working in Levy's lab and first author on the paper, was able to inject live S. epidermidis into the tiny animals' jugular veins, simulating what happens when an IV or catheter infection occurs in an hours-old preemie in the NICU.

The findings surprised the team—and gave hope.

"Newborns have traditionally been considered immunologically immature and distinct from adults in their ability to fight off infection," says Kronforst, now an attending physician in neonatology at Lurie Children's Hospital of Chicago. "Through our model, we have shown that there is a robust inflammatory response to bacterial challenge even at the earliest hours of life. Additionally, we were able to reproduce many clinical features of sepsis that we see in human infants. Because of these features, our model is ideal for exploring novel diagnostic and therapeutic possibilities—something we're extremely excited about."

For example, one part of the inflammatory response, also known to occur in human newborns, was increased production of a molecule called Toll-like receptor-2 (TLR2). Levy's team and others are now evaluating TLR2 as a potential biomarker for detecting sepsis, as well as a potential target for treatments to suppress the inflammation.

"We can now try to block TLR2 in our model, to see if we can clear bacteria faster and prevent inflammatory damage," Levy says.

Even when babies with sepsis are treated with antibiotics, the inflammatory response to the infection can be just as harmful. "Infants spend a lot of energy fighting the infection, and the inflammatory response impairs weight gain," says Levy.

Impaired weight gain was also seen in the mouse model. A separate study with the model, presented at last May's Pediatric Academic Society meeting, linked increased TLR2 production with another kind of damage: impaired development of the brain's white matter.

"There's an emerging literature showing that having bacteria in the bloodstream is harmful to the newborn brain, and that the harms the brain even if the is cleared," Levy says. "That raises the bar tremendously for detection and treatment."

Levy and his colleagues have been invited to apply for funding to develop new treatments using their .

Explore further: Molecular causes for life-threatening fungal infections in case of sepsis unravelled

More information: dx.plos.org/10.1371/journal.pone.0043897

Related Stories

Molecular causes for life-threatening fungal infections in case of sepsis unravelled

July 27, 2012
(Medical Xpress) -- Pathogenic fungi cause infections with a high mortality rate in patients with weakened immune systems. At Karl Kuchler’s CD Laboratory at the MedUni Vienna, the molecular causes of the life-threatening ...

An advance for a newborn vaccine approach

April 13, 2011
(PhysOrg.com) -- Infectious disease is a huge cause of death globally, and is a particular threat to newborns whose immune systems respond poorly to most vaccines. A new approach developed at Children's Hospital Boston, using ...

'Blueprint' for blocking MMP may unlock new treatments for deadly blood infection

May 18, 2011
Researchers studying the life threatening infectious disease sepsis have discovered how the infection can lead to a fatal inflammatory response through blood vessel cells. The research, which is published in EMBO Molecular ...

Streptococci and E. coli continue to put newborns at risk for sepsis

April 25, 2011
Bloodstream infections in newborns can lead to serious complications with substantial morbidity and mortality. What's more, the pathogens responsible for neonatal infections have changed over time. In recent years, however, ...

Recommended for you

Want to win at sports? Take a cue from these mighty mice

July 20, 2017
As student athletes hit training fields this summer to gain the competitive edge, a new study shows how the experiences of a tiny mouse can put them on the path to winning.

'Smart' robot technology could give stroke rehab a boost

July 19, 2017
Scientists say they have developed a "smart" robotic harness that might make it easier for people to learn to walk again after a stroke or spinal cord injury.

Engineered liver tissue expands after transplant

July 19, 2017
Many diseases, including cirrhosis and hepatitis, can lead to liver failure. More than 17,000 Americans suffering from these diseases are now waiting for liver transplants, but significantly fewer livers are available.

Lunatic Fringe gene plays key role in the renewable brain

July 19, 2017
The discovery that the brain can generate new cells - about 700 new neurons each day - has triggered investigations to uncover how this process is regulated. Researchers at Baylor College of Medicine and Jan and Dan Duncan ...

New animal models for hepatitis C could pave the way for a vaccine

July 19, 2017
They say that an ounce of prevention is worth a pound of cure. In the case of hepatitis C—a disease that affects nearly 71 million people worldwide, causing cirrhosis and liver cancer if left untreated—it might be worth ...

Omega-3 fatty acids fight inflammation via cannabinoids

July 18, 2017
Chemical compounds called cannabinoids are found in marijuana and also are produced naturally in the body from omega-3 fatty acids. A well-known cannabinoid in marijuana, tetrahydrocannabinol, is responsible for some of its ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.