Grant: Operating Grant

Severe sepsis (ie. life-threatening infections) is triggered by harmful microorganisms or their toxins in the blood or tissues. These harmful agents damage the lining of blood vessels which can lead to blood clot formation, inflammation, and blood vessel obstruction. In Canada, there are approximately 90,000 patients with severe sepsis each year. Of these, 30 to 50 percent will die. The identification of highly reliable outcome predictors in severe sepsis patients is important for several reasons including: to help describe how sick the patient is, to classify patients for enrolment in clinical studies, and to monitor a patient's response to treatment and procedures. In our lab, we found that high levels of DNA in the blood can predict death better than any other clinical or biological factor. We also have preliminary results which suggest that high levels of DNA in the blood can trigger blood clots and inflammation. In the current proposal, we plan to study how DNA in the blood triggers blood clots and inflammation. We will perform studies of blood cells and blood molecules in the test tube as well as in a mouse model of sepsis. We will also see if removal of DNA in the blood (for example with enzymes that degrade DNA) can improve survival in septic mice. Our research thus has the potential to significantly improve the management and treatment of septic patients.