Navigation Links
Mayo Clinic researchers challenge sepsis theory

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.


Source:Mayo Clinic

Related biology news :

1. Mayo Clinic Researchers Create Obedient Virus; First Step To Use Measles Virus Against Cancer
2. Chronic Sinus Infection Thought To Be Tissue Issue, Mayo Clinic Scientists Show Its Snot
3. Clinical trial to test stem cell approach for children with brain injury
4. Mayo Clinic collaboration discovers protein amplifies DNA injury signals
5. Mayo Clinic researchers discover cancer cells may move via wave stimulation
6. Mayo Clinic study finds two genes predict outcome for breast cancer patients
7. Mayo Clinic Cancer Center: Harnessing the measles virus to attack cancer
8. Mayo Clinic collaboration mining of ancient herbal text leads to potential new anti-bacterial drug
9. Mayo Clinic study suggests that a central nervous system viral infection can lead to memory deficits
10. Mayo Clinic: Gene expression profiling not quite perfected in predicting lung cancer prognosis
11. NYU researchers simulate molecular biological clock
Post Your Comments:

(Date:11/12/2015)...  A golden retriever that stayed healthy despite having ... provided a new lead for treating this muscle-wasting disorder, ... of MIT and Harvard and the University of São ... Cell, pinpoints a protective gene that boosts ... The Boston Children,s lab of Lou Kunkel , ...
(Date:11/10/2015)... 10, 2015 About signature ... helps to identify and verify the identity of ... as the secure and accurate method of authentication ... particular individual because each individual,s signature is highly ... when dynamic signature of an individual is compared ...
(Date:10/29/2015)... --  MedNet Solutions , an innovative SaaS-based eClinical technology ... is pleased to announce that it has been selected ... of only three finalists for a 2015 Tekne ... category. The Tekne Awards honor Minnesota ... and leadership. iMedNet™ eClinical  technology ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... (PRWEB) , ... November 24, 2015 , ... ... maintain healthy metabolism. But unless it is bound to proteins, copper is also ... Health (NIH), researchers at Worcester Polytechnic Institute (WPI) will conduct a systematic study ...
(Date:11/24/2015)... ... ... This fall, global software solutions leader SAP and AdVenture Capital brought together dozens ... BIG ideas to improve health and wellness in their schools. , Now, the top ... of SAP's Teen Innovator, an all-expenses paid trip to Super Bowl 50, and an ...
(Date:11/24/2015)... 2015 /PRNewswire/ - Aeterna Zentaris Inc. (NASDAQ:  AEZS) ... remaining 11,000 post-share consolidation (or 1,100,000 pre-share consolidation) ... B Warrants") subject to the previously disclosed November ... 2015, which will result in the issuance of ... the issuance of such shares, there will be ...
(Date:11/24/2015)... QC , Nov. 24, 2015 /CNW Telbec/ - ProMetic ... "Corporation") announced today that Mr. Pierre Laurin , President ... corporate presentation at the upcoming Piper Jaffray 27 th ... Palace Hotel, on December 1-2, 2015. st ... available for one-on-one meetings throughout the day. The presentation will ...
Breaking Biology Technology: