SEPSIS IMMUNOLOGY
Abstract
Sepsis is a severe systemic infection with organ dysfunction that requires urgent action. With insufficiently prompt and effective intervention, mortality exceeds 30 %. The heterogeneity of sepsis is the reason for the failure of clinical trials of immunomodulatory therapy in patients with sepsis. Due to insufficient understanding of the pathogenetic causes of this heterogeneity, treatments that seemed promising in the preclinical setting have not been successful in clinical trials. The lack of effectiveness is somewhat due to the application of a one-size-fits-all approach to patients with sepsis. Diagnostic and therapeutic strategies that take into account the individual characteristics of the patient are not widely used in the field of sepsis. A shift to more personalized care is needed in all three areas of sepsis management: antibiotic therapy, resuscitation, and organ support. Therefore, attempts are being made to stratify patients into more homogeneous groups based on common prognostic and predictive characteristics of the immune response for the group. This approach is the key to precision medicine, with selection on the basis of pathophysiological mechanism of those patients who are more likely to respond to specific therapy. The problem lies in the relatively limited understanding of the mechanisms governing the immunopathology of sepsis. After decades of research, sepsis remains ill-defined, and no single definition of sepsis captures the complexity of the syndrome. An in-depth analysis of phenotypic differences reveals subgroups of patients who are actually helped by certain interventions. Transcriptome analysis of whole blood, plasma, and individual populations of immune cells identified gene expression signatures that not only distinguish sepsis from non-infectious systemic inflammatory response syndrome, but also distinguish sepsis endotypes with different immune profiles and different responses to therapy, which are determined by the pathobiological mechanism. Thus, there is growing interest in a more individual approach to the management of sepsis, but the best means of implementing it have not yet been identified, so information continues to accumulate.
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