Source: Columbia University
Summary: Researchers have found a clue in understanding how an infection can spiral into sepsis by blunting the body’s immune response.
Sepsis is an infection that kills as many Americans each year as stroke and Alzheimer’s combined-about 250,000-but very little has changed in the treatment of this age-old scourge. It can start with a simple infected cut. When the immune system fails to fight off the infection, sepsis occurs when inflammation spreads throughout the body, leaving patients vulnerable to organ damage, severe secondary infections, and death. While time is of the essence, doctors lack quick, efficient ways to diagnose this deadly condition. The immune system initially launches a vigorous attack against sepsis, but then the innate immune response shuts down. In a search to understand the underlying mechanism, researchers from the Columbia University have found a clue in understanding how an infection can spiral into sepsis by blunting the body’s immune response. The study findings were published in the journal Nature.
The team identified two microRNAs (miR-221 and miR-222) that are produced in immune cells during prolonged inflammation. These microRNAs silence inflammatory gene expression and in a mouse model of sepsis suppress the immune system at a time when the body desperately needs a full immune response. Patients with suspected sepsis had a similar reaction. Among 30 hospitalized patients, those with evidence of organ failure exhibit higher levels of miR-221 and miR-222 in their blood samples. In septic patients, those with elevated miR-221 and miR-222 also exhibited evidence of immunosuppression. With a faster diagnosis, doctors could start antibiotics and fluids to control the infection more quickly before patients succumb to organ failure and secondary infections.
Asst. Prof. Daniel Freedberg said, “When doctors face sepsis in the hospital, it is usually a mystery as to what is causing the infection, but they must act quickly. They can choose to use the broadest spectrum of antibiotics for an aggressive approach to cover every bacterial cause of infection, but this may later cause antibiotic resistance, a growing problem.”
More Information: John J. Seeley et al, “Induction of innate immune memory via microRNA targeting of chromatin remodelling factors”, Nature (2018). DOI: 10.1038/s41586-018-0253-5