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Reviving Immune Cells: A New Approach to Sepsis Treatment

The dysfunction of the immune system can lead to increased vulnerability to infections from various pathogens such as viruses, bacteria, and fungi. Researchers at Radboud University Medical Center have made significant strides in this area, revealing that an already existing drug can reactivate immune cells that are operating suboptimally. This discovery opens avenues for new research focused on patients in intensive care units (ICU) suffering from sepsis.

Sepsis is a critical condition linked to about 20% of global deaths and stands as the leading cause of mortality in ICUs. Characterized by organ failure, such as that of the kidneys or lungs, sepsis arises from a chaotic immune response to infection. Patients afflicted by sepsis often find themselves gravely ill in the ICU, where approximately one-third do not survive. Historically, medical professionals have attributed sepsis-related deaths primarily to an excessive acute immune response that inflicts damage on organs. However, contemporary understanding reveals that a severely weakened immune response, known as immune paralysis, can also significantly contribute to mortality. This condition renders patients unable to combat their current infection and leaves them highly susceptible to new infections, often of fungal origin.

Investigating Immune Responses in Healthy Individuals

The challenge remains for researchers globally to find ways to rectify the impaired immune response seen in sepsis patients. A team from Radboudumc, located in Nijmegen, is undertaking this challenge by studying immune responses in healthy volunteer subjects. They induce a controlled immune response by administering endotoxins, which are components derived from dead bacteria. Utilizing advanced technological methodologies, the research team, including ICU specialist Guus Leijte, meticulously monitored changes in the immune system during both the initial inflammatory phase and the subsequent phase characterized by immune paralysis.

Laboratory investigations led by first author Farid Keramati focused on immune cells extracted from blood and bone marrow of the participants. The observations indicated that monocytes, a type of immune cell, failed to mature properly following the acute immune response, thereby impairing their functionality. Through this analysis, the researchers uncovered a pivotal mechanism responsible for immune paralysis, as these monocytes are crucial in the body’s defense against infections. Keramati, who was affiliated with the Princess Máxima Center during this study, remarked, ‘This comprehensive analysis provided an in-depth understanding of the immune response, offering us vital insights for potential treatments aimed at rejuvenating the body’s compromised defenses against infections.’

Evaluating Medication to Activate Immune Cells

The research team subsequently introduced a known medication, interferon beta, to the monocytes in laboratory conditions. Interferon beta, typically employed in the treatment of multiple sclerosis (MS)—a condition where the immune system’s malfunction leads to inflammation within the central nervous system—showed positive effects on the paralyzed monocytes. Following the drug’s administration, the maturation and functionality of these monocytes improved significantly.

Future Research Directions on Immune Paralysis

Matthijs Kox, the lead researcher, emphasizes the promising nature of these findings but notes that further investigations are crucial. ‘So far, we’ve evaluated the impact of interferon beta on cells within the lab setting. The next phase involves administering this drug to healthy participants during the later stage after endotoxin administration. We aim to assess whether this can effectively counteract immune paralysis.’ Additionally, the potential for future studies will also examine whether interferon beta can enhance the performance of monocytes from patients experiencing sepsis in the ICU. ‘If so, we could be looking at a viable treatment option for these patients,’ Kox added.

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