Researchers determine trauma spills the contents of our cell powerhouses, it can evoke a potentially deadly immune response much like a severe bacterial infection. The study was published in the Journal of Trauma and Acute Care Surgery,
A drug that cleaves escaped proteins called N-formyl peptides appears to reduce resulting dangerous leakage from blood vessels and improve survival. The research drug deformylase, or something similar, may one day be a novel treatment for patients with systemic inflammatory response syndrome, or SIRS, a body-wide inflammatory reaction to trauma or infection, as well as sepsis, a systemic infection when the cause of the infection, like a bacteria, is known.
They are hoping our work will improve the care of trauma and other critically ill patients.
The entire hypothesis behind this and it's called the danger theory is that our mitochondria used to be bacteria so when their contents are released our body treats them like an infection. The results can be pretty much the same as if external bacteria entered our bodies: rapid heart rate, fever, a precipitous drop in blood pressure and swelling. They have also incubated human endothelial cells that line the aorta with N-formyl-rich plasma taken from patients with severe trauma.
Deformylase improved sepsis survival in their animal model by 28% and prevented separation of the tightly knit human endothelial cells that keep blood vessel content contained.
Five years ago, the researchers showed that N-formyl peptides have a powerful relaxant effect in rat arteries that carry blood from the aorta to the gastrointestinal tract. They surmised that when high levels are present, following trauma and another disease, it exacerbates dilation of the arteries and low blood pressure as well as inflammation.
They looked daily at levels of mitochondrial DNA and N-formyl peptides in the fluid of patients with an open abdominal wound following a significant injury. They found that routine flushing of the area significantly reduced levels of N-formyl peptides. They hypothesized then and are now studying whether more frequent flushing can help those patients keep levels low and reduce their risk of SIRS and sepsis.
Current studies have them looking in the peritoneal fluid, blood, and urine at levels of these peptides in patients who are getting the standard irrigation of the area every 48 hours versus every 24 hours. If they find more frequent flushes control the levels, that could be sufficient for patients like these with access.
The author notes that many trauma patients, as well as patients with another tissue-damaging disease like cancer and pneumonia, do not have ready access at the injury site. The current version of deformylase they are using has an extremely short half-life so their many pursuits include a more stable version that could be used clinically for those patients.
According to a study, researchers sepsis is the second leading cause of death in non-coronary care ICUs in the United States, with a mortality rate of up to 45%.