Identification Of Genes Linked To Death From Sepsis In Mice

Sepsis is a life-threatening condition; that arising when the body’s response to infection causing injury to its own tissues and organs. That occuring when the body’s immune response to infection spirals out of control.

But the bacteria in the bloodstream trigger immune cells to release powerful molecules called cytokines to quickly activate the body’s defenses. Sometimes the response goes overboard, creating a so called cytokine storm; that leaves people feverish or chilled, disoriented and in pain. In severe cases, it can lead to multi-organ failure and death.

The study finding a set of genes that help cells survive exposure to cytokines. The genes are involving in disposing of cellular waste, a process known as autophagy. Mice that lack key autophagy genes are more likely to die from sepsis, the study showing.

Genes linked to death

Sepsis is a medical emergency and even with prompt medical care, about 15 percent of people do not survive, while many survivors experience longstanding complications. y systematically inactivating one gene at a time from immune cells in a dish before treating them with interferon gamma, the researchers discovered that cells need a full complement of autophagy genes to survive exposure to the potent cytokine.

Further experiments revealed that a second cytokine, called tumor necrosis factor, was also critical for the accelerated cell death in this system. By injecting mice with tumor necrosis factor; which is to drive the cytokine storm in people.

Autophagy systems

The mice whose autophagy systems were crippling by the absence of important autophagy genes got sick faster and were more likely to die. Chemical compounds that enhance or block autophagy are already being studied by researchers focused on cancer; cardiovascular disease and other conditions. Therapies that suppress autophagy may increase the risk of sepsis.

However, the study showing that if mice lack autophagy; they are sicker and more likely to die. But we think that a better understanding of these processes could lead to attractive targets for developing more effective ways to treat sepsis.