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OBJECTIVE The beneficial effects of metronidazole in intestinal inflammation are generally attributed to the drug's antimicrobial actions. The objective of this study was to determine whether metronidazole exerts an anti-inflammatory action by inhibiting leukocyte-endothelial cell adhesion in postcapillary venules. METHODS Short-term (leukotriene B4 superfusion) and long-term (subcutaneous indomethacin injections) inflammatory responses were elicited in rat mesentery). The number of adherent and emigrated leukocytes, leukocyte rolling velocity, erythrocyte velocity, blood flow, and shear rate were monitored in normal and inflamed postcapillary venules. RESULTS Eightfold and 2.7-fold increases in leukocyte adherence and comparable increments in leukocyte emigration were observed 48 hours and 14 days after indomethacin treatment, respectively. Metronidazole, but not its vehicle (methylcellulose), reversed the leukocyte adherence and emigration responses elicited by indomethacin. The antibiotic was equally effective in preventing the reduction in leukocyte rolling velocity and increased leukocyte adherence/emigration elicited by acutely exposing venules to leukotriene B4. CONCLUSIONS These results indicate that some of the beneficial effects of metronidazole in intestinal inflammation may be related to its influence on leukocyte-endothelial cell adhesion.
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