Abstract
IntroductionThe gut is often considered as the motor of critical illness through bacterial translocation, which amplifies the inflammatory response and alters the immune status. However, systemic bacterial translocation was rarely proven and endotoxin measurement only reflects translocation of Gram-negative-derived products. The process could be more frequently identified if peptidoglycan, derived from both Gram-negative and Gram-positive bacteria, was measured.MethodsWe developed a new tool to detect circulating peptidoglycan-like structure using a NOD2-transfected cell line. We also measured plasma and cell-associated endotoxin and different plasma markers of inflammation. We studied 21 patients undergoing abdominal aortic surgery (AAS), and 21 patients undergoing carotid artery surgery (CAS) were included as negative controls. Patients were sampled during surgery until two days post-surgery.ResultsIn 90.5% of the AAS patients, a NOD2 agonist peak was detected in plasma before aortic clamping, but after gut manipulation by the surgeon, and persisted after blood reperfusion. As expected, no peak was detected in plasma from CAS patients (P = 0.003). Leukocyte-bound endotoxin appeared after blood reperfusion in 71% of the AAS patients, and circulating endotoxin was detected for 57% of them. The levels of interleukin (IL)-6, IL-10 and of inflammatory markers (C-reactive protein, procalcitonin) were maximal at postoperative day 1 or 2 in AAS patients. The levels of circulating NOD2 agonist positively correlated with those of cortisol and IL-10.ConclusionsThe measurement of circulating NOD2 agonist gives a higher informative tool than that of circulating endotoxin for early and sensitive detection of the translocation of bacterial products. The data suggest that circulating NOD2 agonist contributes to further enhance the stress response following surgery.
Highlights
The gut is often considered as the motor of critical illness through bacterial translocation, which amplifies the inflammatory response and alters the immune status
Set-up of the NOD2 agonist detection system To develop a new tool for the detection of circulating NOD2 agonist, we used the HEK293T cell line constitutively expressing NOD2 as a sensor of bacterial PGN through its minimal motif muramyl dipeptide (MDP) [20,21]
Human embryonic kidney (HEK) 293T cells transfected with nucleotidebinding oligomerization domain (NOD) 2 and nuclear factor (NF)- B luciferase expression plasmids were stimulated with MDP or S. aureus PGN
Summary
The gut is often considered as the motor of critical illness through bacterial translocation, which amplifies the inflammatory response and alters the immune status. Systemic bacterial translocation was rarely proven and endotoxin measurement only reflects translocation of Gramnegative-derived products. Endotoxin (lipopolysaccharide (LPS)) is a microbial product commonly measured in the bloodstream, and its levels correlate with survival in patients with sepsis [10]. Levels of circulating endotoxin were shown to correlate with liver function deterioration in patients with cirrhosis [11] or with the occurrence of multiorgan failure in intensive care unit patients [12]. The occurrence of endotoxinemia is more frequent than positive hemocultures, endotoxin being present only in Gram-negative bacteria, its measurement does not reflect the translocation of Gram-positive bacteria-derived. During meningococcal infection, leukocyte-bound LPS was found in all studied patients, whereas circulating endotoxin was detected in only two out of five patients [17]
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