Translocation of bacterial NOD2 agonist and its link with inflammation.
BACKGROUND
The 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.


METHODS
We 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.


RESULTS
In 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.


CONCLUSIONS
The 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.
Kim
Oh Yoen
OY
Cytokines & Inflammation Unit, Institut Pasteur, 28 rue Dr, Roux, 75015 Paris, France. ohkite@hotmail.com
Monsel
Antoine
A
Bertrand
Michèle
M
Cavaillon
Jean-Marc
JM
Coriat
Pierre
P
Adib-Conquy
Minou
M
D000368:Aged; D000369:Aged, 80 and over; D001012:Aorta, Abdominal / Q000601:surgery; D001426:Bacterial Proteins / Q000819:agonists*; D002097:C-Reactive Protein / Q000032:analysis; D002339:Carotid Arteries / Q000601:surgery; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007249:Inflammation / Q000382:microbiology*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000819:agonists* / Q000235:genetics
D001426:Bacterial Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D002097:C-Reactive Protein