Sepsis causes changes in immunity
Assumptions that severe infections make the immune system more resistant to the development of cancer have received scientific confirmation. According to a publication in the journal Nature Immunology, patients who survived sepsis were about 7% less likely to develop cancer than those who had mild infections. These data were obtained by French scientists as a result of large-scale observation of a population of 5 million patients.
The long-term effects of severe infections may not only be negative: for example, the immune systems of sepsis survivors may subsequently fight off cancer. By the way, scientists have been suspecting this for centuries. In 1829, surgeon Guillaume Dupuytren described the case of a woman with extensive breast carcinoma who refused surgery. Eighteen months later she was bedridden, exhausted and nearly dying. At this time, the patient developed a fever and began vomiting. After some time, doctors diagnosed gangrene in the unfortunate woman. But in the end everything ended well. As the famous American geneticist Dmitry Prus says, many doctors of past centuries believed in an antagonistic relationship between infectious diseases and cancer. He writes that doctors eventually agreed that particularly acute childhood infections change the long-term activity of the immune system, helping, among other things, the body cope with certain types of cancer, especially immune-modulated ones such as melanoma. "Among other things" “is a gentle way to mention the many dangerous diseases of autoimmune origin that also develop after similar infectious episodes,” writes Prus.
The authors of a new paper in Nature Immunology note that sepsis causes changes in immunity that persist for several months after recovery. The impact of this immunological reprogramming on cancer risk has until now been unclear. The researchers analyzed patient records from a national database of medical records to show that sepsis survivors had a lower cumulative incidence of cancer than those who had mild infections.
The study included patients hospitalized with pneumonia, strokes or injuries, and they often experienced systemic inflammatory hyperactivation of the immune system due to developing infections. 700 thousand of these patients developed sepsis. In such a large cohort, it was clear that in subsequent years the risk of cancer in sepsis survivors decreased by an average of 7%, and this applied to a wide variety of cancer types. For those who did develop cancer, their course was more favorable.
What was the basis of the “protection” they received? from carcinogenic factors? “At the cellular-molecular level, the authors showed that “permanently resident” cells play a role in anticancer protection. in tissues T-lymphocytes, and they, in turn, are attracted and supported by specialized macrophages. It was also possible to find out something about the cytokines involved in this reprogramming of the immune system after sepsis, and then the authors analyzed in detail the molecular mechanisms of what is happening in a mouse model (with caution noting that sepsis in mice differs in many ways from human sepsis, and not everything has been established on a mouse model, may apply to people),” says Dmitry Prus.
The authors believe that their work demonstrates a therapeutically significant antitumor effect of trained immunity induced by sepsis. And they note that substances are known that can reproduce a similar protective effect for the immune system therapeutically. For example, one of the immune system modulators, simulating the effects of sepsis — laminarin, a polysaccharide from the brown algae kelp, which has been extensively studied in recent years as an anticancer drug. Prus writes that these are the first steps towards an answer to the question posed two centuries ago.
And yet, doctors recommend not to give hope to anyone who has had severe viral infections: much more often than positive effects they produce negative ones, in the form of post-infectious consequences. In addition, sepsis — a very heavy price to pay for a very unreliable effect. In addition, doctors consider it very dangerous to indulge in all sorts of immunomodulators and attempts to “strengthen the immune system.” Don’t think that the “more” We are immune, so much the better, it doesn’t work that way. The immune system consists of many links, each of which plays its own role — and strengthening one or another link can result in both benefit and harm.
Meanwhile, several years ago, the journal Science published a review, “Acute infections as a means of cancer prevention: counteracting chronic infections?” Epidemiological studies have found an inverse association between acute infections and cancer development. They even used the old saying as an illustration: “What doesn't kill me makes me stronger.”
The researchers reviewed the historical literature and examined the latest epidemiological data on the relationship between acute infections and subsequent cancer development in adult life. Scientists have confirmed that childhood infections are associated with a subsequent reduction in the risk of developing certain types of melanoma and ovarian cancer. Acute infections in adults subsequently reduce the risk of meningioma (glioma), melanoma, and overall cancer incidence. Overall, cancer risk reduction increased with increasing frequency of infections, with acute febrile infections providing the greatest protection. However, scientists came to a completely different conclusion regarding chronic infections. Unlike acute ones, they lead to a decrease in immunity and, alas, are associated with an increased risk of development. As they say, not everything is so simple. After all, the same pathogen that causes an acute infection in one person can cause a chronic infection in another.
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