Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers challenge sepsis theory

09.02.2006


Propose new approach for better treatment of deadly condition



A Mayo Clinic research team has challenged the accepted theory on the cause of sepsis -- a condition in which the body’s cells generate fever, shock and often death. Sepsis is thought to occur when poisons from bacterial infection interfere with the cells. The Mayo researchers challenge that long-held concept with a new theory in an opinion piece in the current issue of Trends in Molecular Medicine. Their findings suggest that sepsis begins with a change in certain cellular receptors that then provoke widespread inflammation, even in the absence of bacteria or their poisons.

"We think people have been focusing too exclusively on a single causal factor of sepsis for the last 150 years and, as a result, therapeutically aiming at the wrong target -- the bacteria and the poisons they produce," says senior author Jeffrey Platt, M.D. "That’s why the death rate remains so high despite efforts to block the poisons."


The researchers define a new "first step" that initiates the sepsis syndrome cycle. In this step, a critical receptor for bacterial poisons and for some of the body’s own substances is liberated from "natural suppression." Once free to function, the receptor can trigger the catastrophic cascade of events that is sepsis. The sepsis syndrome can occur during a bacterial infection, as the accepted medical principle holds, or -- as the Mayo Clinic team theory suggests -- it also can occur when substances the body makes act like the bacterial poisons. The Mayo investigators suggest that some or even many cases of sepsis may actually be caused by these normal body substances. The Mayo team argues that this new understanding of how sepsis arises could lead to new treatments for this major medical problem.

Significance of the Mayo Clinic Research

Approximately 700,000 cases of sepsis occur annually in the United States, half of which are fatal. Sepsis is the second most common cause for admissions to critical care units and can be a significant complication of some heart surgeries. The Mayo Clinic researchers believe current sepsis treatment isn’t more effective because the theory of sepsis is too narrow. Current treatments don’t target all causes of sepsis syndrome -- only the bacterial poison cause -- which was described by a 19th century researcher as "the putrid gift."

"Our work is the first to show that this change in receptors in the body is the first true step in the sepsis syndrome, rather than the introduction of a poison," explains Dr. Platt. "The importance then becomes clear. If we really do now have the first cause of sepsis -- not the bacteria, but the unconstrained receptors -- then we can therapeutically interfere with that receptor release mechanism by designing new treatments and possibly, and at long last, develop drugs that treat all cases of sepsis."

Challenging Existing Theories

Dr. Platt and his colleague, Gregory Brunn, Ph.D., say the evidence they’ve published compels this conceptual shift about sepsis. "The problem with the concept of sepsis, and what provoked some of our interest, is that it has been known for 10 years that when you treat with anything that interrupts bacterial poisons, it has no impact on the septic disease. That suggests that perhaps the poisons don’t cause sepsis after all," Dr. Platt says. "Problems such as this caused us to ask, ’Could there be something else driving sepsis, other than the classic poisoning explanation?’"

Mayo Discovers Key Piece of the Puzzle

Dr. Platt and colleagues discovered several years ago that certain naturally-occurring molecules can stimulate receptors once thought to be exclusive for the bacterial poisons (endotoxins). Once stimulated, the receptors (toll-like receptors) set the sepsis cycle into motion. "This finding was very exciting," notes Dr. Platt. "It explained how the sepsis syndrome can occur when there isn’t an infection -- which it does in some cases."

However, Drs. Brunn and Platt saw an obvious problem with this explanation. If normal substances from the body can stimulate toll-like receptors and cause the sepsis syndrome, why aren’t we all desperately ill with sepsis? Dr. Brunn explains, "Our bodies are not poised to respond to sepsis. Our bodies are held in check by the fact that this molecule-receptor system is constrained in its activity. What causes sepsis -- and the syndrome like sepsis that can happen in cancer or trauma or in response to drugs -- is that this receptor gets released from its constraint. That’s the first step that actually initiates sepsis." Research is underway to discover new therapies that could prevent, blunt or reverse the release of the constrained receptor.

Robert Nellis | EurekAlert!
Further information:
http://www.sciencedirect.com/science/journal/14714914
http://www.mayoclinic.org/news

More articles from Health and Medicine:

nachricht Nanoparticles as a Solution against Antibiotic Resistance?
15.12.2017 | Friedrich-Schiller-Universität Jena

nachricht Plasmonic biosensors enable development of new easy-to-use health tests
14.12.2017 | Aalto University

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: First-of-its-kind chemical oscillator offers new level of molecular control

DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.

Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Engineers program tiny robots to move, think like insects

15.12.2017 | Power and Electrical Engineering

One in 5 materials chemistry papers may be wrong, study suggests

15.12.2017 | Materials Sciences

New antbird species discovered in Peru by LSU ornithologists

15.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>