Bromelain as a Biologically-Based Therapy for IBD

描述(申请人提供)：菠萝酶是一种从菠萝茎中提取的蛋白酶的混合物。我们和其他人之前已经证明菠萝酶可以去除影响淋巴细胞迁移和激活的细胞表面分子，并在体外改变分离的白细胞产生细胞因子和炎症介质。据坊间报道，口服菠萝蛋白酶可以缓解两名常规药物治疗无效的溃疡性结肠炎患者。然而，菠萝酶对结肠炎的疗效尚未在动物或人类身上进行严格的测试。我们假设菠萝酶可以通过蛋白水解性去除白细胞和/或结肠细胞上影响炎症性肠病(IBD)的细胞表面分子来降低炎症性肠病的活性。 产生促炎细胞因子和趋化因子。这项研究的具体目的是：1) 确定菠萝酶治疗IBD小鼠模型的疗效；以及2)确定菠萝酶体外治疗对人类结肠活检中存在的细胞产生促炎细胞因子和趋化因子的影响。目前对菠萝酶疗法可能改变IBD炎症活动的潜在机制缺乏了解，这阻碍了主流医学对其认真考虑。拟议的研究将提供临床前疗效和机制数据，这将是未来研究这种基于生物学的补充方法治疗IBD所必需的。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库。

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.