New insights into how the immune system can malfunction during sepsis are reported in a paper published online this week in Nature Immunology. The study demonstrates a new approach for reversing the paralysis of the immune system that characterizes the late stages of sepsis.
Commonly acquired in hospitals and frequently fatal, sepsis is caused by bacteria or fungi that enter the bloodstream. Within a few hours of infection, cells of the immune system become hyperactive and then, days later, the immune system often becomes paralyzed, which makes patients susceptible to other infections. However, the role of white blood cells in the immune response during this later stage of sepsis is poorly understood.
Tom van der Poll, Mihai Netea and colleagues investigated metabolic changes in the white blood cells of 33 patients with bacterial sepsis, 13 patients with fungal sepsis, and 8 healthy volunteers who had agreed to undergo a mild form of experimentally induced sepsis (via injection of low dose that causes only short-term, flu-like symptoms), as well as in an experimental mouse model of sepsis. They found that the inability of white blood cells to respond effectively to bacterial or fungal infections seemed to be caused by a drastic reduction in the cells’ overall metabolic activity. After the patients recovered from sepsis, the normal metabolic activity of their cells of the immune system resumed. The team was also able to restore metabolic activity and responsiveness in white blood cells from patients with fungal sepsis by treating them with interferon-γ - a factor released by normal white blood cells responding in a healthy way.
These distinct and modifiable changes in white blood cell metabolism might represent a potential therapeutic target for effective treatment of this severe condition.