PLATELET-ACTIVATING-FACTOR AND INTERLEUKIN-1 ARE INVOLVED IN COLONIC DYSMOTILITY IN EXPERIMENTAL COLITIS IN RATS

Background: Intracolonic administration of trinitrobenzene sulfonic acid (TNBS) to rats produces chronic colitis associated with an increased release of eicosanoids, platelet-activating factor (PAF), and interleukins. Methods: Motor effects of TNBS on proximal colon were evaluated electromyographically in rats. Mediator involvement was investigated using eicosanoids and PAF antagonists. Results: The colonic myoelectrical activity was 59 ± 17 spike bursts per hour lasting 6.9 ±1.3 seconds. Two to eight days after TNBS treatment, spike-burst duration was significantly (P < 0.05) higher, with a maximal 1.5-4-fold enhancement at day 3. These alterations were significantly (P < 0.05) reduced by daily treatment with MK-886, a 5-lipoxygenase inhibitor (10 mg/kg, orally), whereas indomethacin (1 mg/kg per day, intramuscularly) was ineffective. At day 3, RP55778, a PAF antagonist (45, 60 mg/kg, intraperitoneally), and rIRAP, an interleukin 1 antagonist (0.3 mg/kg, intraperitoneally) but not KT1-32, a thromboxane A2 antagonist (30, 60 mg/kg orally), nor SKF104,353, a leukotriene D4 antagonist (2, 4 mg/kg, orally), significantly (P < 0.05) reduced the TNB-induced motor effects. Conclusion: TNBS-induced colitis in rats involves a delayed long-lasting dysmotility involving PAF, interleukin 1, and some leukotrienes but not leukotriene D4, thromboxane A2, or other cyclo-oxygenase products. © 1993.