Existing drug shows potential to revive immune cells in sepsis patients

When the immune system does not function properly, individuals become more susceptible to infections caused by viruses, bacteria, or fungi. Researchers from Radboud university medical center have demonstrated that an existing drug can revive immune cells that are not functioning correctly. These findings provide leads for further research in patients admitted to the intensive care unit (ICU) with sepsis. 

Twenty percent of global deaths are associated with sepsis, and it is the leading cause of death in ICUs. Sepsis is characterized by organ failure, for instance of the kidneys or lungs, caused by a dysregulated immune response to an infection. Patients with sepsis are often so ill that they end up in the ICU, where about a third of them die. For a long time, doctors believed that sepsis-related mortality was only due to an overly aggressive acute immune response that damages organs. It is now known that mortality can also result from a severely suppressed immune response, known as immune paralysis. Patients with immune paralysis cannot effectively fight their existing infection and are highly vulnerable to new infections, for instance caused by fungi. 

Research in healthy volunteers 

This presents a challenge for researchers worldwide on how to correct the dysregulated immune response in patients with sepsis. To address this, a team of researchers at Radboudumc in Nijmegen studies the immune response in healthy volunteers. They trigger a controlled immune response in these participants by injecting pieces of dead bacteria, called endotoxins. Using advanced technologies, the team, including ICU-researcher Guus Leijte, was able to closely track how the immune system changes during both the acute inflammatory phase and the later phase in which the immune system is paralyzed. 

In the lab, first author Farid Keramati examined the immune cells obtained from the blood and bone marrow of the participants. He observed that certain immune cells, monocytes, did not mature properly after the acute immune response and functioned less well. The researchers thereby identified a crucial mechanism contributing to immune paralysis, as these monocytes play a vital role in the body's defense against infections. Keramati, who was working at the Princess Máxima Center during the study, explains: 'This comprehensive analysis gave us a detailed understanding of what happens during an immune response. This provided us with clues for potential treatments that could revive the body's weakened defense against infections.' 

Medication activates immune cells 

The researchers then added an existing drug, interferon beta, to the monocytes in the lab. This drug is used for the treatment of multiple sclerosis (MS), where the immune system does not function properly, causing inflammation in the central nervous system. Interferon beta had beneficial effects on the paralyzed monocytes. After administering the drug, the monocytes matured and functioned better. 

Follow-up research on immune paralysis 

According to lead researcher Matthijs Kox, these results are promising, but further steps are necessary. 'So far, we have only studied the effect of interferon beta on cells in the laboratory. The next step is to administer this drug to healthy participants during the later phase after administration of endotoxins. We want to investigate if this can counteract immune paralysis.' In another possible follow-up study, the researchers aim to investigate whether interferon beta can improve the function of monocytes from patients with sepsis in the ICU. 'If that's the case, we may have a potential treatment to help these patients,' says Kox.