ACUTE AND CHRONIC EFFECTS OF DIFFERENT BILE-ACIDS ON INDOMETHACIN-INDUCED INTESTINAL INFLAMMATION

The role of bile acids in the pathogenesis of bowel inflammation is un known. The objective of this study was to determine whether urso- (UDC ), cheno- (CDC), and taurochenodeoxycholic acid (TCDC) exert a pro-or antiinflammatory action in the acute and chronic phase of the indometh acin model of a long lasting ileitis in rats. Short-term and long-term inflammatory responses (48 h and 10 days, respectively) after two sub cutaneous indomethacin (Indo) injections were elicited in rat small bo wel and mesentery. To distinguish between common and model-specific ef fects bile acids were tested also in another model of acute inflammati on induced by mesenteric superfusion with leukotriene B-4(LTB4). The n umber of adherent and emigrated leukocytes, leukocyte rolling velocity , and venular wall shear rate were monitored in normal and inflamed po stcapillary venules, and fecal pH of ileal contents which has been sho wn to correlate with degree of inflammation was measured. 6.5- and 2.3 -fold increases in leukocyte adherence and comparable increments in le ukocyte emigration were observed 48 h and ten days after indomethacin treatment, respectively. UDC, CDC, and TCDC (10 mg/kg) given daily fro m Indo administration until the experiment attenuated the leukocyte ad herence and emigration responses elicited by indomethacin in short-and long-term inflammation. This effect was accompanied by a significant increase of fecal pH which had been lowered by indomethacin. None of t he bile acids reduced the LTB4-induced increases in adherence and emig ration. Oral administration of UDC, CDC, and TCDC reduces leukocyte ad hesion and emigration in acute and chronic stages of Indo-induced infl ammation. This could be due to the alkalizing effect of these bile aci ds on fecal pH which has been shown to correlate with a decrease of le ukocyte-endothelial cell interactions but-according to the missing eff ectiveness in another model of intestinal inflammation-not to specific influences on leukocyte-endothelial cell adhesion.