The abnormal lipid spectrum in malignant obstructive jaundice in relation to endotoxin sensitivity and the result of preoperative biliary drainage.
BACKGROUND
Biliary obstruction changes the spectrum of lipoproteins, which are now known to bind and neutralize endotoxin. Postoperative septic complications related to an increased susceptibility to endotoxin occur frequently in patients with obstructive jaundice. The effect of preoperative biliary drainage on changes in the lipoprotein spectrum and its relation to endotoxin sensitivity was studied.


METHODS
Abnormalities in the lipoprotein spectrum were assessed in 15 patients with malignant obstructive jaundice before and 3 weeks after endoscopic biliary drainage. Changes in endotoxin responsiveness were assessed by using endotoxin-neutralizing reagents (anti-CD14 monoclonal antibody, polymyxin B, and recombinant bactericidal permeability increasing protein) to block cytokine production in whole blood cell cultures that were stimulated by cholestatic plasma taken before and after drainage.


RESULTS
Drainage normalized very-low-density, low-density, and high-density lipoprotein cholesterol fractions from, respectively, 43% to 19%, 50% to 65%, and 6% to 16% (P <.01). Ex vivo stimulation of whole blood with predrainage cholestatic plasma was 20-fold higher (P <.001) than with postdrainage plasma. Blocking the endotoxin response during the stimulation with predrainage cholestatic plasma with anti-CD14 monoclonal antibody, polymyxin B or recombinant bactericidal permeability increasing protein resulted in attenuation of the inflammatory response, reducing tumor necrosis factor-alpha levels at least 5-fold.


CONCLUSIONS
Preoperative biliary drainage normalizes the changed lipid profile and the endotoxin-stimulating capacity of cholestatic plasma, and this signifies a change in sensitivity to endotoxin.
Department of Surgery, Academic Medical Center, Municipal Hospital Slotervaart, Amsterdam, The Netherlands.
N
N
Kimmings
M E
ME
Sewnath
W M
WM
Mairuhu
A P
AP
Van Zanten
E A
EA
Rauws
S J
SJ
Van Deventer
D J
DJ
Gouma
D001652:Bile Ducts; D001790:Blood Physiological Phenomena; D002779:Cholestasis / Q000097:blood*; D002784:Cholesterol / Q000097:blood; D004322:Drainage; D004731:Endotoxins / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D008055:Lipids / Q000097:blood*; D008074:Lipoproteins / Q000097:blood; D011300:Preoperative Care; D014280:Triglycerides / Q000097:blood
D004731:Endotoxins; D008055:Lipids; D008074:Lipoproteins; D014280:Triglycerides; D002784:Cholesterol