Rectal dialysate and fecal concentrations of neutrophil gelatinase-associated lipocalin, interleukin-8, and tumor necrosis factor-alpha in ulcerative colitis.
OBJECTIVE
Neutrophil gelatinase-associated lipocalin (NGAL) is a newly described neutrophil lipocalin that may bind the proinflammatory bacterial tripeptide N-formylmethionyl-leucyl-phenylalanine. In situ hybridization and immunohistochemical studies have shown a strong NGAL expression in colonocytes and neutrophils in ulcerative colitis (UC). Because NGAL is highly protease resistant, it should be ideal for in vivo fecal and dialysate studies. Our aim was to investigate the potential of NGAL as a disease activity marker in UC and to compare it with IL-8 and TNF-alpha.


METHODS
Twenty-three patients with UC, 14 with Crohn's disease (CD), 19 patients with acute infectious enterocolitis, and 20 healthy controls were included. The disease activity of UC and CD was scored semiquantitatively. Concentrations of NGAL, IL-8, and TNF-alpha were determined in rectal dialysis fluid, feces, and serum using sandwich enzyme-linked immunosorbent assays. The total protein concentration in feces and dialysate fluid was measured, and the amount of markers was expressed as ng/mg protein.


RESULTS
In healthy controls and non-IBD (irritable bowel disease) colitis, the median values for NGAL in feces were 183 ng/mg protein and 546 ng/mg protein (p < 0.01), respectively. When separating UC into clinical activity groups (remission, mild/moderate, and severe disease activity) the corresponding values of NGAL were 442 ng/mg (p > 0.05), 605 ng/mg (p < 0.02), and 3646 ng/mg (p < 0.001, compared with controls), respectively, and in quiescent colonic CD 368 ng/mg (p > 0.05) and in active stages 751 ng/mg (p < 0.01). NGAL levels in dialysis fluid listed in the same order were: 11 ng/mg for controls, 71 ng/mg (p > 0.05) for non-IBD colitis, 100 ng/mg (p < 0.02), 179 ng/mg (p < 0.01), and 2053 ng/mg (p < 0.001) for UC, and 14 ng/mg (p > 0.05) and 121 ng/mg (p < 0.02) for CD, respectively. Serum NGAL concentrations did not differ between UC and CD in quiescent versus active stages. A significant increase of NGAL in both feces and dialysate with increasing disease activity of UC was found (p = 0.02 and p = 0.003, respectively).


CONCLUSIONS
The NGAL content in rectal dialysate and particularly in feces seems to be a reliable marker for severe disease activity in UC, whereas serum NGAL concentrations do not reflect disease activity.
Nielsen
O H
OH
Department of Medicine CF, Glostrup Hospital, University of Copenhagen, Denmark.
Gionchetti
P
P
Ainsworth
M
M
Vainer
B
B
Campieri
M
M
Borregaard
N
N
Kjeldsen
L
L
D000209:Acute-Phase Proteins; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D002352:Carrier Proteins / Q000032:analysis*; D003093:Colitis, Ulcerative / Q000175:diagnosis* / Q000378:metabolism; D003424:Crohn Disease / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005243:Feces / Q000737:chemistry*; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000032:analysis*; D000071068:Lipocalin-2; D054834:Lipocalins; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism*; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D012007:Rectum / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D000209:Acute-Phase Proteins; D015415:Biomarkers; D002352:Carrier Proteins; D016209:Interleukin-8; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D014409:Tumor Necrosis Factor-alpha