白细胞介素—1β和白细胞介素—8在实验性结肠炎发病中的作 …

研究白细胞介素１β和白细胞介素在结肠炎发病中的作用，观察白细胞介素－１受体拮抗剂对结肠炎的疗效。方法 用３０ｍｇ三硝基苯磺酸＋０．２５ｍｌ体积分数为５０％乙醇制成大鼠慢性实验性结肠炎模型，然后于不同时间点尾静脉注入７ｍｇ／ｋｇ ＩＬ－１ｒａ，进行实验性治疗，以静脉注入３ｍｇ氢化可的松琥珀酸钠作为治疗对照，同时观察治疗前后病变结肠组织学变化，测定结肠髓过氧化物酶和超氧化物歧化酶的活性改变，以原位杂交

The effect of interleukin-1 beta interleukin-8 in the pathogenesis of experimental colitis and evaluation of interleukin-1 receptor antagonist therapy]

OBJECTIVE: To study the effect of interleukin-1 beta and interleukin-8 in the pathogenesis of colitis and evaluate the therapeutic effect of interleukin-1 receptor antagonist(IL-1ra). METHODS: A rat model of chronic experimental colitis was induced by administration of trinitrobenzenesulfonic acid (TNBS, 30 mg) in 50% ethanol 0.25 ml. IL-1ra was then administered intravenously with a dosage of 7 mg/kg at different times. Hydrocortisone (3 mg) i.v. administration was served as control. Tissue expression of IL-1 beta mRNA and IL-8 mRNA was then studied by in situ hybridization before and after IL-1ra administration. Histological examination and tissue myeloperoxidase (MPO) and superoxide dismutase (SOD) activities detection were also made to assess the severity of colitis. RESULTS: An acute inflammation with ulcers, neutrophil infiltration and crypt abscess developed that evolved into a chronic inflammation with abundant fibrous connective tissue hypertrophy at 21 days. And it then recurs only after 10 mg TNBS administration. Activities of MPO and SOD correlated with severity of inflammation. Expression of IL-1 beta mRNA was detected in macrophages in lamina propria and submucosa during the whole period of inflammation. It could be also present in epithelial cells in the 3rd day of colitis. While IL-8 mRNA expression appeared at the 3rd day, and disappeared at 21th day when colitis turned into chronic. After IL-1ra administration, the expression of these two interleukins could not be detected, accompanied with alleviation of histological manifestation, decrease of MPO activity and elevation of SOD activity. CONCLUSIONS: IL-1 beta and IL-8 were involved in the pathogenesis of colitis. IL-1ra has preventive and therapeutic effect to colitis.