Sustained Down Regulation of Plasma Tetranectin Contributes to Liver Injury in Pneumonia-Associated Sepsis

Abstract

Background: It was recently shown that tetranectin (TN) concentration in the plasma of sepsis patients was significantly lower than healthy control and that exogenous TN reduced the mortality rate in septic mice. The aim of this study is to determine whether the reduction of plasma TN is a sepsis-specific host response and its impact on organ dysfunction in sepsis.Methods: The study was conducted in the Sepsis Laboratory at the Huaihe Hospital of Henan University in China. Thirty-seven healthy, 30 community-acquired pneumonia (CAP) and 363 sepsis with comorbid pneumonia (SWP) subjects were recruited. A murine model of polymicrobial sepsis was used to characterize the role of plasma TN in sepsis pathogenesis.Results: TN concentrations in plasma from both CAP and SWP subjects were lower than healthy controls, but not significantly different between male and female sepsis patients, before and after the occurrence or the resolution of sepsis. In addition, plasma TN was not associated with the occurrence of septic shock or sepsis mortality in both genders. On the other hand, plasma TN negatively correlated with liver injury indicators in moribund SWP subjects. In mice of polymicrobial sepsis, a significant decrease in plasma TN occurred within hours after the ligation and puncture of the cecum. Recombinant human TN induced significant reductions of tissue injury markers of liver, but not other organs. In addition, exogenous TN selectively reduced the level of receptor-interacting protein kinase 3 among a panel of cell death markers in septic mouse liver. Conclusions: The dramatic and persistent down-regulation of plasma TN is not a sepsis-specific host response, but contributes to liver injury in pneumonia-associated sepsis.