Eminetra Today (EUA)

Sepsis causes changes in the function of defense cells and can lead to death

Publicado em 12 maio 2021

Article published in Immunology Frontier Sepsis suggests that it can cause changes in the function of defense cells that persist after the patient is discharged. This cell reprogramming causes a disorder that the author calls post-septic syndrome. Symptoms include frequent reinfections, cardiovascular changes, cognitive impairment, poor physical function, and poor quality of life.

This phenomenon explains why so many patients who survive sepsis die earlier after discharge than patients with other illnesses, or suffer from post-sepsis syndrome, immunosuppression, and chronic inflammation.

This article presents a review of a study conducted to investigate cases of septic patients who died within 5 years of discharge.

Sepsis, considered one of the leading causes of death in the intensive care unit, is a life-threatening systemic organ dysfunction caused by an dysregulated response of an organism to infectious pathogens, usually bacteria and fungi. Defense systems damage the body’s own tissues and organs while fighting infectious pathogens.

If it is not recognized and treated promptly, the condition can lead to septic shock and multiple organ failure. Patients with severe COVID-19 and other infections are at increased risk of developing sepsis and dying.

It is estimated that there are approximately 49 million new cases of sepsis worldwide annually. A study of the Septic Prevalence Database (SPREAD), conducted with the support of FAPESP, shows that hospital mortality from septic shock exceeds 40% worldwide and reaches 55% in Brazil.

“A strong immune response due to massive infections and associated cytokine outflow during sepsis can promote irreversible reprogramming of cell metabolism. Cell reprogramming can occur only in leukocytes or bone marrow. Is low. It can occur in some tissues and cells that cause systemic organ dysfunction. […] As eukaryotic cells develop tools to protect themselves from the invasion of microorganisms, bacteria can transfer genetic material to the DNA of host cells. The latter can induce reprogramming of cell biology and metabolism that persists after the infection is cleared, “the researchers said in the article.

According to Raquel Bragante Gritte, co-lead author with Talita Souza-Siqueira, one hypothesis investigated by the group was that metabolic reprogramming begins in the bone marrow, where cells acquire an pro-inflammatory profile.

“Analyzing the patient’s blood sample even three years after leaving the ICU, monocytes were found. [ a type of defense cell ] Activated and ready for battle. They should have been neutral. Monocytes are usually activated only when they are “mobilized” by the tissue, “Gritte told Agência FAPESP. Gritte and Souzashikera are both researchers at the University of Cruzeiro do Sul (UNICSUL) in the state of São Paulo, Brazil.

Research line

The· Immunology Frontier The article was one of the first published by the group on this subject. Co-authors include two doctors and professors at the University of Sao Paulo (USP). Marcel Cerqueira Cesar Machado, Principal Investigator for FAPESP-supported projects. And Francisco Garcia Soriano. Their research line revealed recent findings in the study of post-discharge septic patients. PubMed A major database of references and summaries on the topics of life sciences and biomedicine.

According to Gritte, the group conducted a follow-up study of 62 patients for three years after being discharged from the ICU at a USP university hospital to determine changes in monocytes, neutrophils, lymphocytes, and microRNA. We analyzed and attempted to identify prognostic markers and factors. It is associated with post-septic syndrome.

Our hypothesis is that white blood cells preserve the memory of sepsis. This helps explain why the patient remains ill after being discharged from the hospital. “

Rui Curi, Study Cco-Article author. Curi is a professor at UNICSUL and director of the Butantan Institute.

In the article, researchers suggest that sepsis may produce certain macrophage phenotypes that remain active after discharge. “Reprogramming of cell metabolism is also involved in the functioning and production of various lymphocyte subsets. Several stimuli and conditions, such as the availability of nutrients in the microenvironment, alter lymphocyte metabolism.” They are writing.

According to Gritte, the next step will include a bone marrow study to understand how cells are reprogrammed by sepsis. “We believe that the key to this change lies in the bone marrow,” she said. “But another possibility is that activation occurs in the blood. More detailed research is needed to find the answer.”

The knowledge gained in this study may serve as the basis for developing strategies to minimize or prevent changes after sepsis.

Last year, the World Health Organization (WHO) published its first report on the global epidemiology of sepsis. Much of the burden of sepsis incidence and mortality weighs heavily on low- and middle-income countries, noting the serious lack of population-based sepsis. Data hinders efforts to address the problem, especially in such countries.

The WHO report states that global collaborative efforts to increase funding and research capacity to generate epidemiological evidence for sepsis and rapid and affordable efforts to improve the identification, prevention and treatment of sepsis. We recommend the development of appropriate diagnostic tools.