Associations of glycocalyx damage biomarkers with inflammation and endothelial activation in infection compared to trauma

Background: Ongoing work by our group found differences in endothelial glycocalyx damage (EGD) biomarker expression over time in Emergency Department (ED) patients with infection and trauma. This may be explained by varying levels of inflammation or endothelial activation. Objectives: To explore associations of three EGD biomarkers with inflammatory and endothelial activation biomarkers in patients with infection or trauma. Methods: Banked serum samples were used from patients with simple infection (n = 22), sepsis (43), septic shock (45) and trauma (30) collected at: enrolment in the ED (T0), 1 hour (T1), 3 hours (T3) and 12–24 hours (T24). EGD biomarkers included syndecan-1 (SYN1), syndecan-4 (SYN4), and hyaluronan (HA). Inflammatory biomarkers included interleukin-6 (IL6), interleukin-10 (IL10), neutrophil gelatinase-associated lipocalin (NGAL), resistin (RTN) and C-reactive protein (CRP). Endothelial activation biomarkers included intercellular adhesion molecule-1 (ICAM) and vascular cell adhesion molecule-1 (VCAM). Laboratory methods included ELISA and cytometric bead array. Random effects linear regression was used to explore associations over time. Only significant results (P < 0.05) are presented. Results: SYN1 was positively associated with IL6 (T24 in sepsis, T3 and T24 in trauma). SYN4 was positively associated with IL6 in septic shock (T0, T1 and T3). In contrast, SYN4 was negatively associated with IL6 in simple infection at T24. HA was positively associated with IL6 (T3 in septic shock, T24 in trauma). SYN1 and SYN4 were positively associated with IL10, with no differences between groups or over time. SYN1 and SYN4 were positively associated with RTN and NGAL at multiple time points in the infection groups, however only associations with SYN1 showed change over time. HA was positively associated with RTN at multiple time points (T0 in sepsis, T1, T3 and T24 in septic shock, T3 and T24 in trauma), as well as NGAL (T0, T1 and T24 in sepsis, T24 in septic shock and trauma). SYN4 was positively associated with ICAM at T0, T1 and T3 in trauma, whereas HA had an overall negative association with ICAM and VCAM in trauma. Conclusions: EGD biomarkers showed positive associations with inflammation in the infection groups, varying with biomarker, time point and illness severity. Associations with inflammation in trauma were later in hospitalisation. Only the trauma group showed an association between EGD and endothelial activation. Further investigation into the mechanism of EGD biomarker release in critically ill patients is required.