Changes in endotoxin-binding proteins during major elective surgery: Important role for soluble CD14 in regulation of biological activity of systemic endotoxin

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) mere 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 mi (P < 0.001); more specifically, 17 of 40 samples showed endotoxin levels of greater than 0.2 EU per mi and corresponding reductions in ENC. Soluble CD14 plasma levels were decreased from 5.6 +/- 0.3 to 4.6 +/- 0.3 mu g per mi (P < 0.05). ENC nas 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 mi in the LBL 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 I 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.