Sepsis is a really dangerous, potentially deadly condition that happens when the body starts to attack its own organs and tissues in response to infection.
In order to truly understand the mechanisms behind this scary issue, important improvements have been made but almost 50 million people from all over the world are still affected by it every year.
Even scarier, in 2017, no less than 11 million deaths were registered.
And as if sepsis was not a big enough problem as it is, in the United States, it is also the most expensive medical condition one can experience!
That being said, understanding how exactly an overactive immune response can cause such a fatal reaction is important, and this is what a group of researchers tried to do by looking into how certain bacteria interacts with cells when someone has an infection.
What they were able to find were the very molecules and cells that may be responsible for deaths from sepsis.
In their newly published study, they explain that “The body’s response to infection starts when the immune cells recognize the components of the invading pathogen. These cells release molecules like cytokines that help eliminate the infection. Cytokines are a group of tiny proteins that recruit other cells to the site of infection and of injury. While cytokines play quite an essential role in immune response, an excessive and uncontrolled cytokine production can cause a dangerous cytokine storm associated with sepsis.”
They go on to note that TNF (tumor necrosis factor) stands out among hundreds of cytokines, being the most looked into and potent in the last 50 years of specialized studies.
Normally, TNF encourages beneficial processes including tissue regeneration and cell survival.
That being said, however, the production of TNF has to be regulated in order to avoid inflammation and proliferation of immune cells.
Otherwise, the uncontrolled production of TNF can lead to inflammatory conditions such as rheumatoid arthritis.
But, of course, that is not all as TNF has to be regulated when infected as well as to prevent excessive organ and tissue damage resulting from an overactive immune response and inflammation.
Left uncontrolled while infected, TNF can lead to sepsis!
And while TNF blockers have been shown to treat many autoimmune diseases such as psoriatic arthritis rheumatoid arthritis, and inflammatory bowel disease, they have generally remained “unsuccessful in preventing this cytokine storm that may arise from COVID-19 infections and sepsis.”
The reason why this is the case is simply that it’s still not clear how TNF causes its devastating effects on the body.
Starting from the fact that blood cells that are made in the bone marrow, also known as myeloid cells are major producers of TNF, the team questioned whether or not these cells also mediate TNF-induced death.
“When we injected mice with a deadly dose of TNF, we found that those lacking either TRIF or CD14, proteins typically associated with immune responses to bacterial LPS but not to TNF, had improved survival. Next, we wished to figure out which cells are involved in TNF induced death. When we injected a deadly dose of TNF in mice lacking these proteins in neutrophils and macrophages, two specific types of myeloid cells, mice had reduced symptoms of sepsis and improved survival. This finding positions macrophages and neutrophils as major triggers for TNF-mediated death in mice.”
All in all, according to their findings, TRIF and CD14 can both potentially treat sepsis, being able to reduce both inflammation and cell death.