Butyrate inhibits NF-kappaB activation in lamina propria macrophages of patients with ulcerative colitis.
BACKGROUND
In ulcerative colitis (UC) the activation (i.e. nuclear translocation) of nuclear factor kappa B (NF-kappaB) is an important step in the regulation of cytokines secreted by lamina propria macrophages. Clinical trials suggest anti-inflammatory effects of locally administered butyrate in UC. The potential effects of butyrate on NF-kappaB activation in lamina propria macrophages of UC patients were investigated.


METHODS
Eleven patients with distal UC were treated for up to 8 weeks with butyrate at 100 mM (n = 6) or placebo (n = 5) enemas. At entry and after 4 and 8 weeks, clinical status was noted and intestinal inflammation was graded endoscopically and histologically. Double-staining with antibodies against NF-kappaB (p65) and CD68 was employed to detect NF-kappaB and macrophages, respectively.


RESULTS
In untreated patients, nuclear translocation of NF-kappaB was detectable in virtually all macrophages. Butyrate treatment for 4 and 8 weeks resulted in a significant reduction in the number of macrophages being positive for nuclear translocated NF-kappaB. In addition, butyrate significantly reduced both the number of neutrophils in crypt and surface epithelia and of the lamina propria lymphocytes/plasma cells. These findings correlated with a significant decrease in the Disease Activity Index (DAI).


CONCLUSIONS
The decrease in DAI and mucosal inflammation in butyrate-treated patients is associated with a reduction of NF-kappaB translocation in lamina propria macrophages. Since the inflammatory process in UC is mainly sustained by macrophage-derived cytokines, the known anti-inflammatory effects of butyrate may in part be mediated by an inhibition of NF-kappaB activation in these macrophages.
Lührs
H
H
Dept. of Medicine, Institute of Pathology, University of Würzburg, Germany. h.luehrs@medizin.uni-wuerzburg.de
Gerke
T
T
Müller
J G
JG
Melcher
R
R
Schauber
J
J
Boxberge
F
F
Scheppach
W
W
Menzel
T
T
D000328:Adult; D002087:Butyrates / Q000008:administration & dosage / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000473:pathology; D004733:Enema; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism*
D002087:Butyrates; D016328:NF-kappa B