Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Traumatic injury sets off a 'genomic storm' in immune system pathways

08.12.2011
Massive, consistent changes in inflammatory gene expression seen in trauma, burns

Serious traumatic injuries, including major burns, set off a "genomic storm" in human immune cells, altering around 80 percent of the cells' normal gene expression patterns. In a report to appear in the December Journal of Experimental Medicine, members of a nationwide research collaborative describe the initial results of their investigation into the immune system response to serious injury, findings which have overturned some longstanding assumptions.

"We have discovered there is a highly reproducible genomic response to injury that is essentially the same – no matter the patient's individual genetic background, whether the injury was caused by major trauma or serious burns, or if recovery is rapid or complicated," says Ronald G. Tompkins, MD, ScD, director of the Sumner Redstone Burn Center at Massachusetts General Hospital (MGH) and principal investigator of the study. "When this project was organized more than a decade ago, the question was raised whether responses would differ so much from person to person that no patterns would appear. It is amazing how similar our responses to injuries like serious burns or trauma actually are."

The Inflammation and Host Response to Injury consortium (http://www.gluegrant.org) was established in 2001 to investigate how the human body responds to injury and what factors set off excessive, uncontrolled inflammation that can lead to the overwhelming body-wide infection called sepsis or to multi-organ dysfunction syndrome, a life-threatening failure of vital systems. To lay the groundwork for further studies, the research team analyzed whole-genome expression patterns in white blood cells from 167 patients being treated for severe trauma at seven U.S. hospitals. Blood samples were taken within 12 hours of the injury and several times during the next 28 days. Gene expression pattern changes were tracked and compared with samples from 133 patients treated for serious burns, 37 healthy controls and four volunteers treated with a bacterial toxin that produces brief flu-like symptoms.

The genomic changes seen in the trauma and burn patients were essentially the same, with immediate increased expression of pathways involved with inflammation and with the first-response innate immune system along with simultaneous suppression of adaptive immune pathways. Over time these patterns changed only in terms of intensity and duration, which runs counter to a widely accepted theory that the initial pro-inflammatory response would be followed by an anti-inflammatory response that opens the door to complications like sepsis and organ failure. Instead the only differences between patients with and without complications were in the magnitude of gene expression changes and how long they lasted. Even the volunteers who received bacterial toxin, whose symptoms lasted for only 24 hours, had similar changes in 40 percent of the gene pathways that were altered in the seriously injured patients.

"Burn patients may take months to years to recover from their injuries, while trauma patients who are going to recover usually do so within a month. So it was entirely unexpected that gene expression patterns in burns and trauma patients changed in exactly the same directions 91 percent of the time," Tompkins explains. "Also if you consider two patients with identical injuries from a serious auto accident – a 20-year old who is ready to go home in a week and a 55-year-old who is still in the ICU and on a ventilator at the same point in time – it would be logical to think that the complications suffered by the older patient must have a genome-based difference. But it turns out that the gene expression changes are the same and the only differences is how much they change and how soon they return to normal. There are no new genes or pathways recruited to deal with those serious complications beyond those already involved in the body's basic response to serious injury.

"With this knowledge we can begin to design therapies to promote improvement in patients who would otherwise have complicated recoveries," he adds. "We also can look at whether measuring genomic changes soon after injury can help us predict which patients will recover well and which will need the maximal treatment typically delivered in ICUs, which in addition to being expensive, can sometimes be harmful." Tompkins is the Sumner M. Redstone Professor of Surgery at Harvard Medical School.

The nationwide collaborative program – which includes investigators from 20 academic research centers around the country – is supported by a grant from the National Institute of General Medical Sciences (NIGMS) at the National Institutes of Health. "We funded this nationwide, multidisciplinary team of researchers to explore how the body responds to life-threatening traumatic injury," said Scott Somers, PhD, of the NIGMS. "The scientists have now created a detailed picture of the genomic aspects of this response, and among their findings are some surprises about the role of inflammation that could point to new strategies for treatment."

Celebrating the 200th anniversary of its founding in 1811, Massachusetts General Hospital is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of nearly $700 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, systems biology, transplantation biology and photomedicine.

Sue McGreevey | EurekAlert!
Further information:
http://www.massgeneral.org/

More articles from Life Sciences:

nachricht Flow of cerebrospinal fluid regulates neural stem cell division
21.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Chemists at FAU successfully demonstrate imine hydrogenation with inexpensive main group metal
21.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

Im Focus: Computer-Designed Customized Regenerative Heart Valves

Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.

Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...

Im Focus: Light-induced superconductivity under high pressure

A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.

Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Supersonic waves may help electronics beat the heat

18.05.2018 | Power and Electrical Engineering

Keeping a Close Eye on Ice Loss

18.05.2018 | Information Technology

CrowdWater: An App for Flood Research

18.05.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>