Hiram C. Polk, Jr., MD
Department of Surgery

Response to Injury Rooted in Our Genes
Traumatic injury remains a leading cause of death in the United States. Not only do victims sustain significant damage from the initial trauma, but the immune response and potential infection with associated organ failure can also pose life-threatening issues.

Too Much of a Good Thing
The immune response to injury and infection is a complex process whose efficiency relies not only upon appropriate cellular reactions, but also upon underlying genetic characteristics, which may enhance or diminish susceptibility to life-threatening infection. The immune response to injury is bimodal. The initial monocyte mediated pro-inflammatory state is followed by a compensatory anti-inflammatory state. An over-exuberant pro-inflammatory response to injury or an over-compensatory anti-inflammatory response have both been thought to be associated with the development of multiple organ failure.

Unlocking the Mystery
Why some patients die of overwhelming infection, while others with similar injuries survive without complication, is likely rooted in our genes. The knowledge of how genotype influences cytokine response during inflammation and infection may be critical in identifying groups of patients with a high risk of developing severe infection and multiple organ dysfunction.

Genotyping to Predict Outcome
Our laboratory is currently genotyping clinical specimens and examining polymorphisms in the genes of several pro-inflammatory cytokines, such as IFN-y, IL-12, and IL-18. Because of IFN-y, IL-12 and IL-18 are fundamental in the initiation and regulation of the pro-inflammatory response; we are correlating genotypes with cytokine production and patient outcome. We plan to identify associations between different polymorphisms with these and other genes and assess the ability of multiple genotypes to predict the risk of developing post-injury infection and organ failure.

We are also analyzing monocyte function in elderly trauma victims. Because elderly patients exhibit worse functional outcomes than their younger counterparts, we are assessing the above-mentioned monocytes in elderly trauma victims. Therapeutic augmentation of macrophage function remains attractive.

Recent interest in very tight control of blood sugar, even in non-diabetic intensive care unit patients, suggests a lessening of infection and an improved survival. We are currently studying a variety of cellular immunologic mechanisms for this observation, as well as its potential therapeutic manipulation.