The effects of infliximab on extraintestinal manifestations of TNBS induced colitis in rats

ABSTRACTInflammatory bowel disease (IBD), a chronic condition of the intestine, is associated with numerous extraintestinal manifestations, including hepatic and pancreatic changes. The aim of this study was to investigate the precence of hepatic and pancreatic changes in rats with 2,4,6-trinitrobenzene sulfonic (TNBS) acid induced colitis and the influence of infliximab treatment on colonic, pancreatic and hepatic damage.Fourty Wistar albino rats were allocated into four groups. Group 1: control (sham), Group 2: TNBS-E induced colitis, Group 3: TNBS-E induced colitis + 5 mg/kg infliximab treatment, Group 4: TNBS-E induced colitis+10 mg/kg infliximab treatment. Colitis was induced by intracolonic installation 30 mg of TNBS dissolved in 0,5 ml of 50% ethanol. Infliximab was adminestered subcutanously only groups of 3 and 4. On day 2, 6 at the doses of 5 and 10 mg/kg, respectively. The animals killed on day 7. Plasma TNF-?, IL-1ß, IL-6, IL-10, MPO, MDA, biochemistries, colonic, liver and pancreatic histology were determined. In our study, all doses of infliximab significantly reduced the plasma TNF-?, IL-1ß, IL-6, MPO, MDA levels, suggesting that TNF-?, IL-1ß, IL-6, MPO, MDA plays a significant pathogenic role in this model of colitis as well. Subcutaneous administration of infliximab reduces the inflammatory activity as well as serum TNF-?, IL-1ß, IL-6, MPO, MDA levels in chemical colitis in rats. The microscobic and macroscobic colonic pathological score in group 2, was found to be significantly higher compared to group 1 (p=0,0001), treatment with infliximab significantly decreases the pathological scores. But hepatic and pancreatic damage were not significantly affected by infliximab treatment. The iv dose of infliximab 5 mg/kg is recommended generally but in our study there is no difference between sc dose of infliximab 5 mg/kg and 10 mg/kg except colonic microscobic score. In our experience, hepatic and pancreatic damage of IBD are not responsive to infliximab. The possible effect on extraintestinal manifestations of infliximab must be further investigated both from clinical and experimental points of view.KEY WORDS: TNBS-induced colitis, infliximab, extraintestinal manifestations, inflammatory bowel disease.