Systemic inflammation increases intestinal permeability during experimental human endotoxemia.
Although the gut is often considered the motor of sepsis, the relation between systemic inflammation and intestinal permeability in humans is not clear. We analyzed intestinal permeability during experimental endotoxemia in humans. Before and during experimental endotoxemia (Escherichia coli LPS, 2 ng/kg), using polyethylene glycol (PEG) as a permeability marker, intestinal permeability was analyzed in 14 healthy subjects. Enterocyte damage was determined by intestinal fatty acid binding protein. Endotoxemia induced an inflammatory response. Urinary PEGs 1,500 and 4,000 recovery increased from 38.8 +/- 6.3 to 63.1 +/- 12.5 and from 0.58 +/- 0.31 to 3.11 +/- 0.93 mg, respectively (P < 0.05). Intestinal fatty acid binding protein excretion was not affected by endotoxemia. The peak serum IL-10 concentrations correlated with the increase in PEG 1,500 recovery (r = 0.48, P = 0.027). Systemic inflammation results in an increased intestinal permeability. The increase in intestinal permeability is most likely caused by inflammation-induced paracellular permeability, rather than ischemia-mediated enterocyte damage.
Hietbrink
Falco
F
Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands. F.Hietbrink@umcutrecht.nl
Besselink
Marc G H
MG
Renooij
Willem
W
de Smet
Martin B M
MB
Draisma
Annelies
A
van der Hoeven
Hans
H
Pickkers
Peter
P
D000328:Adult; D019446:Endotoxemia / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000473:pathology*; D008070:Lipopolysaccharides / Q000633:toxicity; D011092:Polyethylene Glycols / Q000378:metabolism; D018746:Systemic Inflammatory Response Syndrome / Q000378:metabolism / Q000503:physiopathology*; D055815:Young Adult
C493404:FABP2 protein, human; D050556:Fatty Acid-Binding Proteins; D008070:Lipopolysaccharides; D016753:Interleukin-10; D011092:Polyethylene Glycols