Deadly inflammation, but no sign of infection

[Guest guest]

Deadly inflammation, but no sign of infection

 

http://www.vetscite.org/publish/items/005800/index.html

 

23 March 2010

 

Deadly inflammation, but no sign of infection

 

It's a medical mystery. A man arrives in a hospital emergency

room with a broken leg, and 2 days later he's burning with fever

and his lungs are so badly inflamed that he needs a ventilator to

breathe. It's as if he's fighting off a serious bacterial

infection-yet he has no open wounds.

Doctors have seen this life-threatening situation-called systemic

inflammatory response syndrome (SIRS)-play out dozens of times.

Until recently, they believed that shock from an injury, such as

a crushed leg or broken pelvis, reduces blood flow to the gut;

this somehow gives bacteria the opportunity to migrate from the

gut into the blood through a major vein in the abdominal lining,

known as the portal vein. Blood infected with bacteria-a

condition known as sepsis-can cause fever, inflammation, and

organ failure. But in the early 1990s, brothers Frederick and

Ernest Moore, surgeons at the University of Colorado, Denver,

placed catheters in the portal veins of trauma victims with SIRS

and saw no bacteria. Experts now largely agree that such patients

aren't infected, leaving the inflammation unexplained. " No one

could find the source, " says Carl Hauser, a trauma surgeon and

immunologist at Harvard Medical School in Boston.

 

In a new study, Hauser and colleagues focused on plasma, the

colorless fluid in which blood cells are suspended. They took

samples of the fluid from 15 seriously injured patients who had

just arrived in an urban emergency room. The samples contained a

surprising amount of DNA.

Specifically, the researchers found 1000 times more mitochondrial

DNA-the genetic material belonging to the cell's power

plants--than that seen in normal plasma. The data suggest, says

Hauser, that when many cells are damaged in an injury, they

release a large amount of mitochondrial debris into the blood.

" That was the eye-opener for me. "

The body responds to this mitochondrial DNA as if it's a

bacterial invader. When the team exposed human neutrophils, the

dominant type of white blood cell involved in the body's immune

response, to bits of mitochondria, the immune cells launched the

same chemical response that they do when they spot foreign

bacteria. What's more, when the researchers injected

mitochondrial debris into the abdominal lining of mice,

neutrophils swarmed to the site. And in rats, injecting

mitochondrial debris into the blood stream caused lung

inflammation, the team reports in a recent issue of Nature. The

neutrophils were " treating the mitochondria like an enemy, "

Hauser says.

 

The response makes sense. Neutrophils are programmed to recognize

a cluster of molecules known as formyl peptides, which are common

in bacteria and other single-celled organisms. The problem is

that mitochondria, which biologists think were once symbiotic

bacteria, also have these alarm-raising markers. The findings

could lead to better treatments for SIRS. Inflammatory

complications of injury or illness account for about half the

patients in intensive care units, Hauser says, but antibiotics

work only when bacteria are to blame. He says that blocking the

neutrophil response is already possible. But before doctors call

off the body's attack, he says, they need fast, highly accurate

tests that can distinguish a mitochondria-induced inflammation

from real infection. Frederick Moore, now at the Methodist

Hospital Research Institute in Houston, Texas, agrees that the

work provides a way toward more effective treatment of systemic

inflammation. " What clinicians are faced with right now is they

can only do one thing, which is to give patients broad spectrum

antibiotics, " a strategy that is both expensive and potentially

dangerous, he says, as it grows resistant strains of bacteria.

 

ScienceNow

March 23, 2010