Circulating Chemerin and Its Kinetics May Be a Useful Diagnostic and Prognostic Biomarker in Critically Ill Patients with Sepsis: A Prospective Study

Abstract

Chemerin, a novel adipokine, is a potent chemoattractant molecule with antimicrobial properties, implicated in immune responses. Our aim was to investigate circulating chemerin and its kinetics, early in sepsis in critically ill patients and its association with severity and prognosis. Serum chemerin was determined in a cohort of 102 critically ill patients with sepsis during the first 48 h from sepsis onset and one week later, and in 102 age- and gender-matched healthy controls. Patients were followed for 28 days and their outcomes were recorded. Circulating chemerin was significantly higher in septic patients at onset compared to controls (342.3 ± 108.1 vs. 200.8 ± 40.1 μg/L, p < 0.001). Chemerin decreased significantly from sepsis onset to one week later (342.3 ± 108.1 vs. 308.2 ± 108.5 μg/L, p < 0.001), but remained higher than in controls. Chemerin was higher in patients presenting with septic shock than those with sepsis (sepsis onset: 403.2 ± 89.9 vs. 299.7 ± 99.5 μg/L, p < 0.001; one week after: 374.9 ± 95.3 vs. 261.6 ± 91.9 μg/L, p < 0.001), and in nonsurvivors than survivors (sepsis onset: 427.2 ± 96.7 vs. 306.9 ± 92.1 μg/L, p < 0.001; one week after: 414.1 ± 94.5 vs. 264.2 ± 79.9 μg/L, p < 0.001). Moreover, patients with septic shock and nonsurvivors, presented a significantly lower absolute and relative decrease in chemerin one week after sepsis onset compared to baseline (p < 0.001). Based on ROC curve analyses, the diagnostic performance of chemerin (AUC 0.78, 95% CI 0.69–0.87) was similar to C-reactive protein (CRP) (AUC 0.78, 95% CI 0.68–0.87) in discriminating sepsis severity. However, increased chemerin at sepsis onset and one week later was an independent predictor of 28-day mortality (sepsis onset: HR 3.58, 95% CI 1.48–8.65, p = 0.005; one week after: HR 10.01, 95% CI 4.32–23.20, p < 0.001). Finally, serum chemerin exhibited significant correlations with the severity scores, white blood cells, lactate, CRP and procalcitonin, as well as with biomarkers of glucose homeostasis, but not with cytokines and soluble urokinase-type plasminogen activator receptor (suPAR). Circulating chemerin is increased early in sepsis and its kinetics may have diagnostic and prognostic value in critically ill patients. Further studies are needed to shed light on the role of chemerin in sepsis.

G-Trap Assay II: Characterization of blood Leukocyte Functionality differentiates immune activation and immune suppression in bacteremia patient samples

“…45, 46 Proinflammatory cytokines are frequently cited as bacteremia biomarkers in the literature. 2, 24, 47-52 In our previous study 1 we showed how this interplay between circulating pro-and anti-inflammatory cytokines impacted the magnitude of the correlated GTPase signals. Thus, GTPase activity in patient leukocytes represents an integrated signaling outcome reflecting the composition of circulating cytokines due to infection.…”

Chemerin as Potential Biomarker in Pediatric Diseases: A PRISMA-Compliant Study

“…Circulating chemerin is increased in the early stages of sepsis, especially in patients with septic shock, according to recently published data. Moreover, correlations between chemerin and white blood cells, lactates, CRP and procalcitonin as well as biomarkers of glucose homeostasis were observed [21].…”

“…which it binds [20]. In an animal model, chemerin promoted the adhesion of macrophages to extracellular matrix proteins and adhesion molecules, suggesting its involvement in enhancing the inflammatory response [21]. On the other hand, in the case of acute lung injury, this adipokine affects the reduction of the inflammatory process by reducing neutrophil infiltration and inflammatory cytokine release [22].…”

“…Based on the literature, chemerin may be both a proinflammatory and anti-inflammatory molecule, depending on the enzymes involved in the chemerin cleavage, the target cell type and the receptors with which it binds [20]. In an animal model, chemerin promoted the adhesion of macrophages to extracellular matrix proteins and adhesion molecules, suggesting its involvement in enhancing the inflammatory response [21]. On the other hand, in the case of acute lung injury, this adipokine affects the reduction of the inflammatory process by reducing neutrophil infiltration and inflammatory cytokine release [22].…”

Future Perspectives in the Diagnosis and Treatment of Sepsis and Septic Shock

“…Numerous molecules, such as cytokines and chemokines, involved in the inflammatory cascade in sepsis are being studied to identify better-performing biomarkers [ 7 , 8 ]. In this context, certain adipokines (cytokine-like molecules derived from the adipose tissue) have been recently shown to have diagnostic value in sepsis, while their kinetics early in sepsis were found to be independent predictors of sepsis outcome in prospective observational studies [ 9 , 10 , 11 , 12 , 13 , 14 ]. Moreover, advances in proteomics have supported the investigation of a high number of molecules (the so-called secretome) that are produced and secreted during sepsis [ 15 , 16 ].…”