PHENOTYPING OF SYSTEMIC INFLAMMATORY RESPONSE BASED ON IL-6, IL-10 AND TNF-α LEVELS AFTER CARDIAC SURGERY

The systemic inflammatory response after cardiac surgery is characterized by pronounced immunological heterogeneity and the simultaneous operation of pro-inflammatory and compensatory anti-inflammatory mechanisms, which complicates early risk assessment and the selection of personalized therapy. Our study reports dynamic phenotyping of the immune response in patients undergoing planned operations of the heart and/or aorta based on the levels of key cytokines. There was an emphasis on longitudinal changes in cytokine profiles and transitions between them. This prospective single-center study included sixteen adult patients. Venous blood was collected at five time points: before surgery, after the admission to the intensive care after the intervention, and on the first, third, and sixth postoperative days. Concentrations of interleukin-6, interleukin-10, and tumor necrosis factor alpha were measured using the enzyme-linked immunosorbent assay, followed by hierarchical clustering of normalized values. Clustering quality was assessed by the mean silhouette coefficient and by visual analysis of the dendrogram and heat map. Based on relative cytokine levels, four immune phenotypes were identified: hyperinflammatory, adaptive, immunosuppressive, and immune exhaustion, along with an additional group with an indeterminate profile. At study entry, the immunosuppressive phenotype predominated, whereas the hyperinflammatory, adaptive, and immune-exhaustion phenotypes were less frequent and occurred at approximately similar rates. By the sixth day, the proportion of patients with an indeterminate profile increased. Individual longitudinal analysis in the subgroup of patients with a complete set of time points demonstrated both stability of the immunosuppressive state in certain patients and multidirectional transitions, including potentially favorable trajectories from hyperinflammatory to adaptive phenotypes and unfavorable trajectories from adaptive to hyperinflammatory or to indeterminate profiles. The limitations of the study include the small sample size, the single-center design, and the descriptive nature of the analysis, which necessitate confirmation of the results in expanded cohort studies. In conclusion, the data indicates that a substantial proportion of patients exhibited an immunosuppressive phenotype already at study entry, which correlates with contemporary views on the parallel evolution of pro- and anti-inflammatory processes in the postoperative systemic inflammatory response.