Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


New study finds on/off switch for septic shock

According to a new study, septic shock--a dangerous, often deadly runaway immune response--is controlled by a genetic on/off switch. The research also suggests how a drug might temper sepsis. This is the first time this genetic mechanism has been revealed in an experimental animal.

The study by Robert Schneider, Ph.D., the Albert B. Sabin Professor of Microbiology and Molecular Pathogenesis at NYU School of Medicine and his colleagues, is being published in the November 15th print edition of the journal Genes & Development

A killer and a protector

Septic shock is the nation's 10th most frequent cause of death and the leading cause of hospital-related mortality. Bacterial infection, notably the toxins that are part of the bacterial cell wall, stimulate the inflammatory response which can spin out of control. Sepsis progresses swiftly from chills, fever and shallow breathing, to dilated and leaky blood vessels, a lack of blood supply in the body's organs, multiple organ failure and, often, death.

Infection causes the body's immune system to produce protective proteins called cytokines. Problems arise when the body is unable to turn off cytokine production and they overwhelm the body, says Dr. Schneider. "The resulting cytokine storm is, for example, what kills people when they are infected with anthrax and, we think, an important factor in what killed people in the flu pandemic of 1918," he says.

Dr. Schneider and his colleagues focused on one of the key genes that regulate cytokine production called auf1, which has been extensively studied in tissue culture but not in animals. In an attempt to move the research closer to the clinical setting, the team genetically engineered and bred mice lacking the auf1 gene, a so-called knock-out mouse. Then, mice with the gene and mice without it were exposed to a bacterial toxin that causes mild food poisoning. The normal mice had little problem fending off the endotoxin. "The mice without the gene died due to an uncontrolled septic-shock like response--their blood vessels burst, their spleens were destroyed," says Dr. Schneider. Mortality was five-fold higher in mice without the auf1 gene.

Further research showed where auf1 functions at the molecular level, he says. In normal mice, the scientists found that auf1 steps into action once the immune response is activated and after cytokine production gets underway. The action is pronounced: messenger RNAs (mRNAs) which are blueprints for very specific cytokines--namely interleukin-1 beta, tumor necrosis factor alpha and COX-2--are degraded. That process of degrading the mRNAs shuts off production of these cytokines.

In the study, mice lacking the auf1 gene do not seem to have that off switch; their cytokine levels were greatly elevated. A cytokine storm had caused sepsis in these animals.

In summary, auf1 is a protector that can stop an infection from progressing to septic shock, explains Dr. Schneider. It does so by helping with cytokine production and then tempering the production of these proteins. Auf1 acts like a cytokine on/off switch.

The future possibilities

Dr. Schneider believes auf1 makes an excellent target for the development of therapeutics. For example, a drug could turn on auf1 or stabilize its activity as a way to specifically tone down production of those cytokines that are the major players in sepsis, he says. His study results might also help explain why many previous sepsis drug trials have failed. The cytokine storm needs to be turned off at its source, he says, and auf1 offers the on/off switch to do just that.

Jennifer Choi | EurekAlert!
Further information:

More articles from Studies and Analyses:

nachricht Diagnoses: When Are Several Opinions Better Than One?
19.07.2016 | Max-Planck-Institut für Bildungsforschung

nachricht High in calories and low in nutrients when adolescents share pictures of food online
07.04.2016 | University of Gothenburg

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

New method increases energy density in lithium batteries

24.10.2016 | Power and Electrical Engineering

International team discovers novel Alzheimer's disease risk gene among Icelanders

24.10.2016 | Life Sciences

New bacteria groups, and stunning diversity, discovered underground

24.10.2016 | Life Sciences

More VideoLinks >>>