Navigation Links
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, was published in the November 3, 2006 advance online 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.


Related medicine news :

1. Tomato Sauce reduces Cancer Risk- Study
2. Study on obesity and heart failure
3. National Lung Study in the process
4. Study casts doubt on keyboard ills
5. Study reveals how stress can make you sick
6. Study reveals how stress can make you sick
7. Study supports vegetable diet
8. Study to look at early surgery to treat epilepsy
9. Its Never Too Late to Stop Smoking,Study Finds
10. New Technique to Study Infants Brain.
11. Groundbreaking Study Gives Hope For Patients With Kidney Cancer
Post Your Comments:

(Date:6/25/2016)... ... June 25, 2016 , ... Experts from the American Institutes ... Research Meeting June 26-28, 2016, at the Hynes Convention Center in Boston. , ... advance care planning, healthcare costs and patient and family engagement. , AIR researchers ...
(Date:6/25/2016)... ... 25, 2016 , ... As a lifelong Southern Californian, Dr. Omkar Marathe earned ... the David Geffen School of Medicine at UCLA. He trained in Internal Medicine at ... fellowship in hematology/oncology at the UCLA-Olive View-Cedars Sinai program where he had the opportunity ...
(Date:6/24/2016)... ... 24, 2016 , ... Those who have experienced traumatic events may suffer from ... avenues, such as drug or alcohol abuse, as a coping mechanism. To avoid this ... coping following a traumatic event. , Trauma sufferers tend to feel a range of ...
(Date:6/24/2016)... ... June 24, 2016 , ... ... micro-osteoperforation for accelerated orthodontic treatment. Dr. Cheng has extensive experience with all areas ... , AcceleDent, and accelerated osteogenic orthodontics. , Micro-osteoperforation is a revolutionary adjunct ...
(Date:6/24/2016)... ... June 24, 2016 , ... The ... recognize Dr. Barry M. Weintraub as a prominent plastic surgeon and the network’s ... the world, and the most handsome men, look naturally attractive. Plastic surgery should ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... June 24, 2016  Collagen Matrix, Inc., ("Collagen ... and manufacturing of collagen and mineral based medical ... that Bill Messer has joined the ... further leverage the growing portfolio of oral surgery, ... Bill joins the Collagen Matrix executive team ...
(Date:6/24/2016)... 24, 2016 The Academy of Managed Care ... that would allow biopharmaceutical companies to more easily ... make formulary and coverage decisions, a move that addresses ... medicines. The recommendations address restrictions in the ... the drug label, a prohibition that hinders decision makers ...
(Date:6/24/2016)... 24, 2016   Pulmatrix, Inc ., (NASDAQ: ... inhaled drugs, announced today that it was added to ... its comprehensive set of U.S. and global equity ... an important milestone for Pulmatrix," said Chief Executive Officer ... of our progress in developing drugs for crucial unmet ...
Breaking Medicine Technology: