The research team zeroed in on white blood cells, which help fight infection and disease and trigger inflammation. The scientists analyzed the activity of tens of thousands of genes from these cells, which were taken from the volunteers at regular intervals over 24 hours. Because this research plots the course of the inflammatory response over time, it is particularly valuable, according to Scott D. Somers, Ph.D., NIGMS program director of this glue grant. "In the case of injury, time is critical. To provide the best treatment, doctors need to know how the human body responds in the moments and days after an injury," he said. "No other study of injury or inflammation has tracked changes to the entire human genome over time."
The research team found that, of the 5,000 or so genes that fluctuated in response to endotoxin, more than half were turned down, causing the blood cells to be less metabolically active. This seems surprising, as one would expect genes required for healing to be turned up and for white blood cells to be more, not less, active. Although other research groups have seen similar genetic results in animals, scientists don't yet have an explanation for this counterintuitive response.
Understanding inflammation requires knowing not just which genes are involved, but how those genes interact with each other. To investigate this, the group turned to a knowledge base compiled by Ingenuity Systems, Inc. of Mountain View, Calif., that includes 200,000 published reports on more than 8,000 human, rat and mouse genes and their genetic interactions. This tool enabled the group to uncover about 300 genes and several genetic pathways not previously known to be involved in inflammation.
The Nature article is the second in a planned series of papers that aim to improve understanding of the human response to injury. In its first paper, published in March in the Proceedings of the National Academy of Sciences