Bromelain as a Biologically-Based Therapy for IBD

描述（由申请人提供）：菠萝蛋白酶是源自菠萝茎的蛋白酶的混合物。 我们和其他人以前已经表明，菠萝蛋白酶去除影响淋巴细胞迁移和激活的细胞表面分子，并通过体外分离的白细胞改变细胞因子和炎症介质的产生。据报道，口服菠萝蛋白酶可缓解2例常规药物治疗无效的溃疡性结肠炎。然而，菠萝蛋白酶在结肠炎中的功效尚未在动物或人类中进行严格测试。我们假设菠萝蛋白酶可以通过蛋白水解去除白细胞和/或结肠细胞上的细胞表面分子来降低炎症性肠病（IBD）的活性， 促炎细胞因子和趋化因子的产生。本研究的具体目的是：（1） 确定菠萝蛋白酶治疗在IBD的鼠模型中的功效;和2）确定体外菠萝蛋白酶治疗对人结肠活组织检查中存在的细胞产生促炎细胞因子和趋化因子的影响。目前对菠萝蛋白酶治疗可能改变IBD炎症活性的潜在机制缺乏了解，阻碍了主流医学对其进行认真考虑。拟议的研究将提供临床前疗效和机制数据，这对于这种补充性生物学方法治疗IBD的未来研究是必要的。因此，这项研究将加强为补充和替代医学实践提供信息所需的生物医学研究知识基础。

DESCRIPTION (provided by applicant): Bromelain is a mixture of proteinases derived from pineapple stem. We and others have previously shown that bromelain removes cell surface molecules that affect lymphocyte migration and activation and alters the production of cytokines and inflammatory mediators by isolated leukocytes in vitro. Oral bromelain was anecdotally reported to induce remission of ulcerative colitis in two patients who were refractory to conventional medical therapy. However, the efficacy of bromelain in colitis has not yet been tested rigorously in either animals or humans. We hypothesize that bromelain can decrease the activity of inflammatory bowel disease (IBD) by proteolytically removing cell surface molecules on leukocytes and/or colonic cells that affect production of pro-inflammatory cytokines and chemokines. The specific aims of this study are to: 1) To determine the efficacy of bromelain treatment in murine models of IBD; and 2) To determine the effect of in vitro bromelain treatment on production of pro-inflammatory cytokines and chemokines by cells present in human colon biopsies. Current lack of knowledge about potential mechanisms by which bromelain therapy may modify inflammatory activity in IBD has hindered its serious consideration by mainstream medicine. The proposed studies will provide pre-clinical efficacy and mechanistic data that will be necessary for future studies of this complementary biologically-based approach to treatment of IBD. This research will thus strengthen the biomedical research knowledge base needed to inform the practice of complementary and alternative medicine.