While the body's immune and inflammatory responses are vital to fighting off infections, in severe cases where bacteria and its toxic products enter the bloodstream, the body may overreact with a systemic release of proteins that cause inflammation and could result in circulatory failure. The result is called septic shock, and it is a common threat for a wide range of patients, from those with serious respiratory or urinary tract infections, to cancer patients undergoing chemotherapy.
When bacteria seriously infect a body, one of the body's response may be for the arteries to inflame, or swell in size. Like water pressure suddenly switching from a garden hose to a larger pipe, the blood pressure in the arteries dramatically drops. Vital organs such as the brain, lungs, heart and kidney, suddenly are not receiving enough blood. In approximately half the cases of septic shock, the patient dies.
Researchers at Princess Margaret Hospital's Ontario Cancer Institute (OCI), and the Amgen Research Institute, have been studying the IRAK-4 gene to see what it does within the body. "We discovered that when the gene IRAK-4 was deleted from test mice, we effectively tamed the inflammatory response of the mice and prevented septic shock," said the study's lead author, Dr. Wen-Chen Yeh, a principal investigator at OCI and the Amgen Research Institute, and assistant professor at the University of Toronto. "Mice that lacked the IRAK-4 gene were completely resistant to septic shock that is triggered by a lethal dose of toxic bacteria product."
Further study is needed to determine if this is the best gene to target for possible future treatment, said Dr. Yeh. "It is important to caution that this is just one step in a very long process, although it may be an important one," said Dr. Yeh. "There have been many world-wide pioneering discoveries along the path leading to this finding, and there will likely be more after this one."
This research work was done in collaboration with Tularik Inc., and has been supported in part by the National Cancer Institute of Canada with funds from The Terry Fox Foundation. Princess Margaret Hospital and its research arm, Ontario Cancer Institute, have achieved an international reputation as global leaders in the fight against cancer. Princess Margaret Hospital is a member of the University Health Network, which also includes Toronto General Hospital and Toronto Western Hospital. The Amgen Research Institute is an integral part of AMGEN, the world's largest biotechnology company and an innovative and pioneering world-wide organization dedicated to the research and development, manufacture and marketing of human proteins for therapeutic use, using recombinant DNA technology.
For more information, please contact :
Vince Rice, Communications Specialist, Public Affairs,
Princess Margaret Hospital 416-946-4501, ext. 5771
Journal
Nature