Elevated Plasma Levels of Gas6 Are Associated with Acute Lung Injury in Patients with Severe Sepsis.

Abstract

Acute lung injury (ALI) is one of the complications of severe sepsis, causing sudden deaths. However, information regarding predictive factors for the onset of ALI in severe sepsis is limited. Growth arrest-specific gene 6 (Gas6) is secreted by endothelial cells and is important for the activation of endothelium during inflammation. This study aimed to investigate the predictive effect of plasma Gas6 in patients with severe sepsis. Collection of plasma samples was carried out from 129 participants with severe sepsis following with or without ALI development. We found that the elevated levels of Gas6, interleukin-6 and -8 (IL-6 and IL-8) in plasma were associated with the ALI development (P = 0.003, 0.002, and 0.004, respectively). We also observed the robust correlation between the plasma level of Gas6 and the following ALI development to adjustment for sepsis and administration of vasopressor. Between patients with ALI (n = 18) and those without ALI (n = 111), Gas6 and the Lung Injury Prediction Score (LIPS) showed promising discrimination (AUROC, 0.74 and 0.68, respectively), and in combination with these two indexes, the AUROC was increased to 0.86 (vs. 0.74, P = 0.05), while soluble receptor for advanced glycation end products (sRAGE) and Willebrand factor (vWF) in plasma showed no predictive value for of ALI. Collectively, our findings indicate that higher levels of Gas6 in plasma are obviously correlated with ALI development. An early increase in the plasma Gas6 level suggests that endothelial injury is a key link in the pathogenesis of ALI.