Keith J C, Albert L, Sonis S T, Pfeiffer C J, Schaub R G
Genetics Institute, Inc., Cambridge, Massachusetts.
Stem Cells. 1994;12 Suppl 1:79-89; discussion 89-90.
Recombinant human interleukin 11 (rhIL-11) is a pleiotropic cytokine that stimulates bone marrow stem cells to proliferate and decreases intestinal mucosal injury produced by cytoablative drugs and radiation in animals. The effects of rhIL-11 were studied in a hamster model of oral mucositis and in two rat models of inflammatory bowel disease (IBD). Oral mucositis was induced in male Golden Syrian hamsters with 5-fluorouracil 60 mg/kg intraperitoneal, days 0 and 2. Peak mucositis occurred by day 10 in vehicle treated animals. rhIL-11, given twice daily subcutaneously, decreased the mucositis in a dose-dependent manner and increased animal survival at all doses tested. In two models of IBD, the acetic acid-induced acute colonic injury model in Sprague-Dawley rats and the transgenic Fischer 344 rats expressing human HLA-B27 and beta 2-microglobulin, rhIL-11 decreased the gross and microscopic damage in the colons of these animals. These data suggest that rhIL-11 exerts effects on the gastrointestinal mucosa which ameliorate responses to injurious stimuli.
重组人白细胞介素11(rhIL-11)是一种多效细胞因子,可刺激骨髓干细胞增殖,并减少细胞毒性药物和辐射在动物体内造成的肠黏膜损伤。本研究在仓鼠口腔黏膜炎模型以及两种大鼠炎症性肠病(IBD)模型中探究了rhIL-11的作用。于第0天和第2天给雄性叙利亚金黄仓鼠腹腔注射60mg/kg的5-氟尿嘧啶,诱导口腔黏膜炎。在给予赋形剂处理的动物中,第10天出现黏膜炎高峰。每天皮下注射两次rhIL-11,呈剂量依赖性减轻黏膜炎,并提高所有测试剂量下动物的存活率。在两种IBD模型中,即Sprague-Dawley大鼠的乙酸诱导急性结肠损伤模型以及表达人HLA-B27和β2-微球蛋白的转基因Fischer 344大鼠模型中,rhIL-11减轻了这些动物结肠的大体和微观损伤。这些数据表明,rhIL-11对胃肠道黏膜具有作用,可改善对损伤性刺激的反应。