Inflammation is a coordinated response to bacterial and viral infections, involving the activation of white blood cells through receptors on their cell membranes. Normally, this process is highly regulated. However, if an imbalance occurs, complications can arise, such as sepsis, which is an excessive inflammatory response promoted by infections. During sepsis, an intense immune response is triggered, and a cascade of inflammatory molecules are released. Read More
The body then releases anti-inflammatory substances to protect itself, which suppress the immune system. However, this ‘counter response’ increases the risk of tissue and organ damage, and makes the patient more prone to secondary infections. Sepsis can be very serious, and in many cases is fatal. Although some of the cellular responses involved in sepsis have been identified, the exact mechanisms are not completely understood. The varied molecular nature of sepsis also means that treatment can be extremely challenging.
Dr Juan José Martínez-García at the University of Murcia in Spain, alongside colleagues at the affiliated University Hospital, investigated the expression of the P2X7 receptor on white blood cells from patients with serious abdominal infections. This receptor recognises extracellular ATP, which is considered a danger signal. The team wished to find out whether this receptor may help to explain how sepsis progresses inside the human body.
While most studies have focused on the later stages of sepsis, Dr Martínez-García and team decided to concentrate on the cells involved in the early response. They collected white blood cells from patients who had been recently diagnosed with sepsis following abdominal infections, and measured the amount of the target receptor on them. Then, they assessed whether the presence of the receptor was correlated with other indicators of inflammation.
Previously, the researchers had discovered that metabolic changes in the white blood cells of sepsis patients could happen very early in the process. They thought that this may play an important role in the later suppression of the immune system.
During this study, the researchers found that levels of the P2X7 receptor significantly increased during sepsis in a wide variety of blood cell types. Additionally, the higher receptor levels were linked with various inflammatory markers, some of which were detectable in the blood. Interestingly, the team also discovered that the percentage of healthy white blood cells decreased as receptor levels increased.
These findings could have a considerable impact on clinical outcomes, since Dr Martínez-García and his team have identified a potential therapeutic target. This insight could be crucial when designing new treatments for sepsis. Such treatments might involve strengthening white blood cells to improve survival rates.
The team’s important research reveals a likely underlying molecular mechanism for sepsis development, which may prove vital in optimising diagnostic tests, maximising treatment options, and improving patient survival.
