title: Lactulose and neomycin attenuate leukocyte-endothelial cell adhesion in an animal model of inflammatory bowel disease.
abstract: OBJECTIVE
  The role of intestinal flora in the pathogenesis of inflammatory bowel disease is under discussion. The objective of this study was to assess the effect of lactulose (Lac) and neomycin (Neo), both of which are used clinically for changing or reducing intestinal flora, on leukocyte-endothelial cell interaction in an indomethacin (Indo)-induced long-lasting ileitis in Sprague-Dawley rats.
  
  
  METHODS
  Two doses of Indo (7.5 mg/kg, s.c.) were given 24 h apart. Animals were fed with standard rat chow for 10 days until 12 h prior to the experiment. Solutions of Lac (1.0 mg/kg b.w.) or Neo (0.1 g/kg) were gavaged daily for 10 days between Indo administration and the experiment. Ten mesenteric venules (30 microm diameter) per animal (n = 5 per group) were observed using intravital microscopy, and the following parameters were monitored: number of adherent and emigrated leukocytes, leukocyte rolling velocity, erythrocyte velocity, venular blood flow, and shear rate. Macroscopically visible injury was scored 0 to 5, and faecal pH was measured in the distal 20 cm of ileum.
  
  
  RESULTS
  Ten days after Indo treatment leukocyte adherence and emigration were increased (2.2-fold and 3.3-fold vs. control, respectively) while leukocyte rolling velocity and venular wall shear rate were reduced (both parameters to 81% of control). Lac and Neo attenuated microcirculatory parameters to a similar extent while macroscopic damage was prevented only by Neo but not by Lac. The effects of both substances were accompanied by a normalization of faecal pH to control level which had been lowered by Indo.
  
  
  CONCLUSIONS
  The Indo-induced increase in leukocyte-endothelial cell interaction is blunted by Lac and Neo. At the same time the Indo-induced lowering of faecal pH is normalized by both substances. The reduction of macroscopic injury by Neo but not by Lac in the chronic phase of Indo inflammation might be due to additional effects on other inflammatory cells such as macrophages.
authors.affiliation: Department of Internal Medicine I, University of Regensburg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Arndt
authors.forename: J
authors.initials: J
authors.lastname: Schölmerich
authors.forename: K D
authors.initials: KD
authors.lastname: Palitzsch
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002448:Cell Adhesion; D002450:Cell Communication; D004195:Disease Models, Animal; D004727:Endothelium / Q000502:physiology; D005765:Gastrointestinal Agents / Q000494:pharmacology; D007079:Ileitis / Q000473:pathology; D007082:Ileum / Q000098:blood supply; D007213:Indomethacin; D007249:Inflammation; D015212:Inflammatory Bowel Diseases / Q000473:pathology*; D007792:Lactulose / Q000494:pharmacology*; D007962:Leukocytes / Q000502:physiology; D008297:Male; D008833:Microcirculation; D009355:Neomycin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000900:Anti-Bacterial Agents; D005765:Gastrointestinal Agents; D007792:Lactulose; D009355:Neomycin; D007213:Indomethacin