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Sepsis: a new approach for better treatment

Researchers at the Mayo Clinic have 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.
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. " 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.

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 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."