Butyrate Inhibits NF-κB Activation in Lamina Propria Macrophages of Patients with Ulcerative Colitis

Abstract

Background: In ulcerative colitis (UC) the activation (i.e. nuclear translocation) of nuclear factor kappa B (NF- s B) 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- s B 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 s B (p65) and CD68 was employed to detect NF- s B and macrophages, respectively. Results: In untreated patients, nuclear translocation of NF- s B 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- s B. 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- s B 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- s B activation in these macrophages.