The wingless-related integration site-5a/secreted frizzled-related protein-5 system is dysregulated in human sepsis

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 proinflammatory wingless-related integration site (wnt)-5a/anti-inflammatory secreted frizzled-related protein (sFRP)-5 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 proinflammatory wnt5a and wnt5a inhibitor sFRP5 were measured in serum samples by enzyme-linked immunosorbent assay (ELISA) at admission to the intensive care unit (ICU) and 5 days later. Sixty sepsis patients were included, and 30 healthy individuals served as controls. Wnt5a levels were found to be increased significantly in septic patients compared to healthy controls (221 +/- 033versus 032 +/- 003ng/ml, P<00001). In contrast, sFRP5 was not altered significantly in septic patients (1972 +/- 306 versus 1748 +/- 638ng/ml, P=007). On admission to the ICU, wnt5a levels exhibited a significant positive correlation with the leucocyte count (r(s)=03797, P=0004). Interestingly, in patients recovering from sepsis, wnt5a levels declined significantly within 5 days (217 +/- 038-103 +/- 028ng/ml, P<001). In contrast, if sepsis was worsening, wnt5a levels increased in the same time-period by trend (234 +/- 059-325 +/- 102ng/ml, P>005). sFRP5 levels did not change significantly 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.