Explaining Variable Signs of Sepsis
When bacteria or other microbes enter the bloodstream they can trigger the activation of numerous host defenses as part of a process known as inflammation. While inflammation can promote the clearance of the invading microbes, it can also cause collateral damage to the body’s own cells and tissues. In extreme cases, the inflammatory pathways used by the body may spiral out of control, resulting in a life-threatening condition known as sepsis that can lead to organ failure and rapid death.
Sepsis kills well over 250,000 people each year in the United States and is the most expensive condition to treat in hospitalized patients. Patients with sepsis are especially difficult to manage because the signs and symptoms of the disease can vary greatly between individuals. In patients with sepsis, the infecting microbes are usually viewed as generic triggers of inflammation while the patients themselves are considered the primary variables that affect disease progression and severity.
This viewpoint is challenged by new work published in the April issue of the journal mSphere by researchers in the Department of Pathology at the University of Utah School of Medicine. The study shows that variations in just a single bacterial protein known as flagellin can significantly alter levels of inflammation and the progression of sepsis. Much of this work used a novel zebrafish infection model that mimics many of the key aspects of sepsis seen in human patients.
A better understanding of how different flagellin variants differentially affect host inflammatory responses may help researchers develop improved diagnostic and therapeutic tools for sepsis and related diseases. Use of the zebrafish sepsis model may also facilitate the discovery of new treatments that can restore balance to out-of-control inflammatory pathways.