Injuries, Septic Shock, and Inflammation in Men and Mice

Karen Elkins, PhD

Karen Elkins, PhD

By Karen Elkins, PhD, a biomedical scientist and science writer currently working in the field of microbiology and immunology.

How does the physiology of the human body respond to severe injuries and septic shock? Funded by NIH, over 50 researchers have been working on a decade-long set of large projects to analyze human tissues taken directly from seriously ill patients. The goal of this ambitious effort is to understand the body-wide inflammation that accompanies major injuries like trauma with blood loss, major burns, and septic shock from invasive bacterial infections.

In a recent study from this program, researchers analyzed a series of blood samples obtained from three groups of people. Some suffered traumatic injuries with major blood loss, others sustained serious burns, and a few willing volunteers received bacterial endotoxin in order to mimic septic shock. In parallel, researchers also evaluated blood samples from mice that, while anesthetized, were subjected to similar injuries in all three categories. All of the genes in blood cells were then analyzed to determine how their activities changed over time, compared to genes in blood cells from healthy people or mice. The results were pretty dramatic, and surprising: gene activities in people who suffered trauma changed in very similar ways to those who experienced burns, and those patterns were also fairly similar to volunteers treated with endotoxin. The patterns also agreed well with those seen in several other studies of human infections and inflammation.

But the study also found that the gene activities in the three different groups of mice were not very similar to each other, nor to the corresponding injuries in humans. The title of the February 2013 research article, reporting these results in the Proceedings of the National Academy of Sciences USA, emphasized these differences: “Genomic responses in mouse models poorly mimic human inflammatory diseases.” So did the opening paragraph of the resulting New York Times article, which included the line, “Researchers report evidence that the mouse model has been totally misleading for at least three major killers – sepsis, burns and trauma.”

Scientists acknowledge that all models – and all research studies – have their limits, and don’t expect studies in animals to reflect all features of human injuries. Nonetheless, there are many examples of discoveries that started in mice and proved directly applicable to humans, including ones related to inflammation and immunity.

And in this case, the focus on mice distracted from the really intriguing observations in humans, which potentially have big implications. Instead of being a chaotic and unmanageable storm, inflammation after injury might be more like a coordinated weather front, with common responses moving through these insults.

Such life-threatening injuries are very difficult to manage, and costly. But painstaking genomic research like this continues to hold the promise to better understand these conditions, and ultimately provide new treatments that save lives. These sophisticated studies deserve sustained federal funding.

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