The wnt5a/sFRP5 system is dysregulated in human sepsis.

Dominik M Schulte, Dominik Kragelund, Nike Müller, Imke Hagen, Gunnar Elke, Andrea Titz, Dirk Schädler, Jennifer Schumacher, Norbert Weiler, Burkhard Bewig, Stefan Schreiber, Matthias Laudes
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Clinical and experimental immunology : an official journal of the British Society for Immunology
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Sepsis and type 2 diabetes exhibit insulin resistance as a common phenotype. In type 2 diabetes we and others have recently provided evidence that alterations of the pro-inflammatory wnt5a/anti-inflammatory sFRP5 system are involved in the pathogenesis of insulin resistance. The aim of the present study was to investigate whether this novel cytokine system is dysregulated in human sepsis which may indicate a potential mechanism linking inflammation to metabolism. In this single-centre prospective observational study, critically ill adult septic patients were examined and pro-inflammatory wnt5a and wnt5a inhibitor sFRP5 were measured in serum samples by ELISA at admission to the intensive care unit (ICU) and 5 days later. 60 sepsis patients were included and 30 healthy individuals served as controls. Wnt5a levels were found to be significantly increased in septic patients compared to healthy controls (2.21±0.33 ng/ml vs. 0.32±0.03 ng/ml, p<0.0001). In contrast, sFRP5 was not significantly altered in septic patients (19.72±3.06 ng/ml vs. 17.48±6.38 ng/ml, p=0.07). On admission to the ICU, wnt5a levels exhibited a significant positive correlation with the leukocyte count (rs=0.3797, p=0.004). Interestingly, in patients recovering from sepsis, wnt5a levels significantly declined within 5 days (2.17±0.38 ng/ml to 1.03±0.28 ng/ml, p<0.01). In contrast, if sepsis was worsening, wnt5a levels increased in the same time period by trend (2.34±0.59 ng/ml to 3.25±1.02 ng/ml, p>0.05). sFRP5 levels did not significantly change throughout the study period. The wnt5a/sFRP5 system is altered in human sepsis and might therefore be of interest for future studies on molecular pathophysiology of this common human disease.