Changes in Endotoxin-Binding Proteins during Major Elective Surgery: Important Role for Soluble CD14 in Regulation of Biological Activity of Systemic Endotoxin

Abstract

Assessment of circulating endotoxin during the perioperative period, which is only demonstrated by the Limulus amebocyte lysate (LAL) test, may be modulated by several endotoxin-binding proteins. Endotoxin-neutralizing capacity (ENC) and the plasma levels of soluble CD14 (sCD14), lipopolysaccharide-binding protein, and bactericidal/permeability-increasing protein (BPI) were determined in 40 patients 6 h prior to skin incision for major abdominal surgery. The bioactivity of plasma endotoxin was tested by the polymyxin B-inhibited stimulatory activity of the plasma samples on healthy monocytes as measured by the release of tumor necrosis factor alpha. Plasma endotoxin levels in almost all patients increased from 0.05 ± 0.01 to 0.23 ± 0.03 experimental units (EU) per ml (P < 0.001); more specifically, 17 of 40 samples showed endotoxin levels of greater than 0.2 EU per ml and corresponding reductions in ENC. Soluble CD14 plasma levels were decreased from 5.6 ± 0.3 to 4.6 ± 0.3 μg per ml (P < 0.05). ENC was strongly correlated with the sCD14 plasma concentration throughout the period of observation. The addition of sCD14-neutralizing monoclonal anti-sCD14 antibodies reduced ENC both pre- and postoperatively. No correlation could be established between ENC and the plasma levels of BPI, high-density lipoproteins, or low-density lipoproteins determined by measuring the concentrations of apoprotein A and apoprotein B. Biologically active endotoxin was found in only 6 of 17 samples with endotoxin levels greater than 0.2 EU per ml in the LAL test. These samples could be characterized by their perioperative loss of at least 35% of their sCD14. No change in sCD14 was detected in the remaining 11 samples. The perioperative loss of ENC is partly caused by the loss of sCD14 resulting from its consumption by endotoxin reaching the bloodstream. This study demonstrated the role of sCD14 on the bioactivity of circulating endotoxin in a human model of endotoxemia after major abdominal surgery.

Increased serum levels of lipopolysaccharide and antiflagellin antibodies in patients with diarrhea‐predominant irritable bowel syndrome

“…The serum level of sCD14 was inversely correlated with the serum level of LPS in our study. This finding can possibly be explained by a loss of sCD14 from consumption by LPS reaching the bloodstream as showed before by Hiki et al . Funderburg et al .…”

Manipulation of the small intestine as a cause of the increased inflammatory response after open compared with laparoscopic surgery

“…Previous studies have demonstrated that loss of gut barrier function together with bacterial and endotoxin translocation might be major causes of postoperative acute‐phase reactions after abdominal surgery17–19. In the present study, only animals in the open group showed significant portal and systemic endotoxaemia after gastrectomy.…”

“…Small‐bowel manipulation during abdominal surgery can initiate an intense local inflammatory response12–15 and cause distant organ damage16. Previous studies have demonstrated that loss of gut barrier function together with bacterial and endotoxin translocation might be the major cause of postoperative acute‐phase reactions after abdominal surgery17–19. Surgical manipulation during laparoscopic procedures causes only minor trauma to the peritoneal environment and this could minimize the inflammatory response in the gut that results in bacterial or endotoxin translocation.…”

Effect of the Synbiotic (<i>B. animalis </i>spp. <i>lactis </i>Bb12 + Oligofructose) in Obese Subjects. A Randomized, Double-Blind, Controlled Clinical Trial

“…In the present study, we determine plasma sCD14 and LBP rather than plasma endotoxin considering the short half-life of plasma LPS in humans (about 3 hours), compared with those of sCD14 and LBP (24-48 h), that indicates that plasma sCD14 and LBP probably reflect long-term LPS exposure while plasma LPS could reflect the transient kinetics of LPS absorption only. In agreement with this, the release of sCD14 by cultured peripheral blood monocytes has been shown to increase significantly in the presence of low stimulatory LPS concentrations (0.01 ng/ml), suggesting that sCD14 may be considered as a biomarker of LPS exposure [44,45]. Our results show that the synbiotic treatment did not improve the plasma concentrations of usCRP, IL-6 and LBP while it contributes to maintain lower plasma concentrations of sCD14 during the study compared with the control group.…”