Increased intestinal permeability and altered mucosal immunity in cholestatic jaundice.
OBJECTIVE
To examine the effects of cholestatic jaundice on gut barrier function.


BACKGROUND
Gut barrier failure occurs in animal models of jaundice. In humans, the presence of endotoxemia indirectly implicates failure of this host defense, but this has not previously been investigated in jaundiced patients.


METHODS
Twenty-seven patients with extrahepatic obstructive jaundice and 27 nonicteric subjects were studied. Intestinal permeability was measured using the lactulose-mannitol test. Small intestinal morphology and the presence of mucosal immunologic activation were examined in endoscopic biopsies of the second part of the duodenum. Systemic antiendotoxin core IgG antibodies and serum interleukin-6 and C-reactive protein were also quantified. Intestinal permeability was remeasured in 9 patients 5 weeks after internal biliary drainage.


RESULTS
The median lactulose-mannitol ratio was significantly increased in the jaundiced patients. This was accompanied by upregulation of HLA-DR expression on enterocytes and gut-associated lymphoid tissue, suggesting immune activation. A significant increase in the acute phase response and circulating antiendotoxin core antibodies was also observed in the jaundiced patients. After internal biliary drainage, intestinal permeability returned toward normal levels.


CONCLUSIONS
A reversible impairment in gut barrier function occurs in patients with cholestatic jaundice. Increased intestinal permeability is associated with local immune cell and enterocyte activation. In view of the role of gut defenses in the modern paradigm of sepsis, these data may directly identify an important underlying mechanism contributing to the high risk of sepsis in jaundiced patients.
Welsh
F K
FK
Department of Pathology, St. James's University Hospital, Leeds, England.
Ramsden
C W
CW
MacLennan
K
K
Sheridan
M B
MB
Barclay
G R
GR
Guillou
P J
PJ
Reynolds
J V
JV
D000210:Acute-Phase Reaction; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000032:analysis; D002463:Cell Membrane Permeability / Q000276:immunology; D001651:Cholestasis, Extrahepatic / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D004322:Drainage; D004731:Endotoxins / Q000276:immunology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007413:Intestinal Mucosa / Q000276:immunology / Q000503:physiopathology*; D007792:Lactulose / Q000378:metabolism; D008297:Male; D008353:Mannitol / Q000378:metabolism; D008875:Middle Aged; D015607:Stents; D015854:Up-Regulation
D000906:Antibodies; D004731:Endotoxins; D008353:Mannitol; D007792:Lactulose