Treating sepsis by protecting blood vessels shows promise
No specific treatment is currently available for sepsis — also referred to as blood poisoning or septicemia — a life-threatening condition that affects 19 million people worldwide every year. Now, a new study shows that protecting blood vessels from the damage caused by sepsis could be a way to successfully treat a condition that poses a major challenge in the intensive care unit.
In the journal Science Translational Medicine, researchers from South Korea describe how their approach — which targets the body’s vascular response as opposed to the infection itself or the body’s inflammation response — stopped mice from succumbing to sepsis.
The treatment uses an unconventional antibody that converts a normally harmful protein into a protective one.
Sepsis is a serious medical condition caused by an overwhelming immune response to infection; it eventually damages the body’s organs by depriving them of nutrients and oxygen. In the worst cases, patients spiral toward septic shock and multiple organs — lungs, kidneys, liver — may quickly fail and cause death.
The condition — which is more common than heart attacks — is a leading cause of hospital deaths. In the US, severe sepsis strikes more than a million Americans every year, and estimates suggest between 28–50% of affected patients die — a higher number than deaths from prostate cancer, breast cancer and AIDS combined.
Sepsis does not arise on its own but stems from other medical conditions, such as an infection in the urinary tract, skin, lungs, abdomen (such as appendicitis) or other part of the body. Invasive medical procedures that accidentally introduce bacteria into the bloodstream can also bring on sepsis.
The study shows that protecting blood vessels from the damage caused by sepsis could be a way to successfully treat the potentially life-threatening condition.
‘Strengthen the blood vessels’
One of the first things that happens in sepsis — when the immune system overreacts and attacks the body — is that blood vessels become weak and leaky. This results in a cascade of life-threatening effects, ranging from severe inflammation and organ damage, to pulmonary edema (fluid in the lungs) and death itself.
There is currently no cure for sepsis; doctors are only able to target the underlying infection and hope that patients can find the strength to fight the sepsis on their own.
The approach that the researchers behind the new study take is also not exactly a cure for sepsis, but one that attempts to prevent and protect the blood vessels from its worse effects and thus improve the odds that the body can deal with the sepsis.
One of the study authors, Dr. Seung Jun Lee, a researcher at the Institute for Basic Science in Daejeon, South Korea, says the purpose of the treatment is to “strengthen the blood vessels so the body has a stable environment to fight the infection which also prevents further damage.”
The method focuses on activating a receptor protein — called TIE2 — that sits on the surface of cells in the lining of blood vessels. When activated, TIE2 boosts the ability of the blood vessel lining to prevent inflammation and leakage.
Antibody simultaneously blocks ANG2 and activates TIE2
Earlier attempts to boost the effect of TIE2, or reduce the effect of ANG2 — a protein that blocks TIE2 — have either not been very effective or are impractical for clinical use.
In the new study, the team used an antibody called ABTAA (short for ANG2-binding and TIE2-activating antibody) that works by simultaneously blocking ANG2 and activating TIE2. In their paper, the researchers describe how it works:
“Upon binding to ANG2, ABTAA triggers clustering of ANG2, assembling an ABTAA/ANG2 complex that can subsequently bind and activate TIE2.”
Thus, by binding to it, ABTAA converts the normally harmful ANG2 into a protein complex that boosts a protective effect.
In three different mouse models of sepsis, treatment with ABTAA prolonged survival better than conventional ANG2 blockers.
The researchers also found that combining ABTAA antibody treatment with antibiotics further enhanced survival from sepsis caused by bacterial infection.
Fast facts about sepsis
- Sepsis is on the rise in the US
- Anyone can get it, but it is more common in people with weakened immune systems, children, infants and the elderly
- Sepsis is the most expensive condition treated in US hospitals, costing more than $20 billion in 2011.