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Translocation of bacterial NOD2 agonist and its link with inflammation

Oh Yoen Kim1, Antoine Monsel, Michèle Bertrand

  • 1Cytokines & Inflammation Unit, Institut Pasteur, 28 rue Dr, Roux, 75015 Paris, France. ohkite@hotmail.com

Critical Care (London, England)
|July 30, 2009
PubMed
Abstract

Insights

A new method to detect bacterial products in the gut, using a NOD2 agonist, is more effective than endotoxin measurement for identifying bacterial translocation after surgery and understanding the stress response.

Area of Science:

  • Gastroenterology and immunology
  • Sepsis and critical illness research
  • Surgical inflammatory response

Background:

  • Bacterial translocation from the gut is a key factor in critical illness, amplifying inflammation and altering immune status.
  • Current methods for detecting bacterial translocation, like endotoxin measurement, are limited as they only detect Gram-negative products.
  • Measuring peptidoglycan, present in both Gram-negative and Gram-positive bacteria, offers a more comprehensive approach to identifying bacterial translocation.

Purpose of the Study:

  • To develop and validate a novel tool for detecting circulating peptidoglycan-like structures using a NOD2-transfected cell line.
  • To compare the efficacy of NOD2 agonist detection with endotoxin measurement in identifying bacterial translocation post-surgery.
  • To investigate the correlation between bacterial product translocation and inflammatory markers, cortisol, and the stress response following surgery.

Main Methods:

  • A new assay utilizing a NOD2-transfected cell line was developed to detect circulating peptidoglycan-like structures (NOD2 agonist).
  • Plasma and cell-associated endotoxin levels, alongside inflammatory markers (IL-6, IL-10, CRP, procalcitonin), were measured.
  • The study included 21 patients undergoing abdominal aortic surgery (AAS) and 21 undergoing carotid artery surgery (CAS) as controls, with samples collected from surgery up to two days post-operatively.

Main Results:

  • A NOD2 agonist peak was detected in 90.5% of AAS patients before aortic clamping and persisted post-reperfusion, unlike in CAS patients (P = 0.003).
  • Leukocyte-bound endotoxin was observed in 71% and circulating endotoxin in 57% of AAS patients post-reperfusion.
  • Circulating NOD2 agonist levels positively correlated with cortisol and IL-10, indicating a link to the stress response.

Conclusions:

  • Detection of circulating NOD2 agonist is a more sensitive and earlier indicator of bacterial product translocation than endotoxin measurement.
  • The findings suggest that circulating NOD2 agonist plays a role in exacerbating the stress response following major surgery.
  • This novel detection method provides a valuable tool for understanding gut-mediated inflammatory processes in critical illness and surgical patients.

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