LEUKOCYTE-ENDOTHELIAL CELL-ADHESION IN INDOMETHACIN-INDUCED INTESTINAL INFLAMMATION IS CORRELATED WITH FECAL PH

Background-Recent studies indicate that faecal pH is acidified in pati ents with inflammatory bowel disease compared with healthy controls. I n healthy volunteers, stool pH, faecal flora, and bile acid concentrat ion could be affected by means of elemental diets. Aims-To assess the role of variations of faecal pH on leucocyte endothelial cell adhesion in indomethacin induced long lasting ileitis in rats. Methods-Indomet hacin (7.5 mg/kg subcutaneously) was injected twice, 24 hours apart. R ats were either fed with the identical diet before and 10 days after t he induction of inflammation until the experiment, or the diet was cha nged at the time of induction. Ten postcapillary mesenteric venules (3 0 mu m diameter) per animal were observed using intravital microscopy. Macroscopic visible intestinal ulceration was scored and faecal pH of different sections of the small bowel was determined. Results-Small i ntestinal faecal pH was 8.5 in controls and 8.0 in indomethacin treate d animals. Indomethacin significantly changed microcirculatory paramet ers: there was a 2.3-fold increase in leucocyte adherence, a 3.2-fold increase in leucocyte emigration, and a 20% reduction in shear rate. A pplication of various diets or diet combinations resulted in variation s in faecal pH ranging from 7.8 to 8.8 which were inversely correlated with macroscopic ulcerations (r=-0.67). Leucocyte adherence was atten uated with increased pH and augmented with decreased pH (r=-0.55). Ven ular wall shear rate was positively correlated with faecal pH (r=0.48) while leucocyte emigration showed no correlation. Leucocyte rolling v elocity was not significantly altered. Normalisation of faecal pH by d ifferent alkalising drugs induced a significant decrease in leucocyte adherence in standard fed, indomethacin treated rats. Conclusions-Faec al pH is lowered in the indomethacin model of long lasting ileitis in rats, which is similar to human inflammatory bowel disease. Alkalisati on of faecal pH due to different diets or alkalising drugs reduces ind omethacin induced leucocyte endothelial cell adhesion and macroscopic intestinal damage. These results may provide a rationale for the thera peutic effect of enteral diets in disease.