Scientific Abstract

Proposal No.  IBD-0024R
Principal Investigator:  Laura P. Hale, M.D., Ph.D.
Applicant Organization:  Duke University (Durham, North Carolina, U.S.A.)
Project Title: Bromelain treatment of inflammatory bowel disease
Period of Award:  December 1, 2003 - February 28, 2005

Bromelain is a naturally derived mixture of proteinases that is marketed as a “digestive aid” in health food stores.  Recently, bromelain was anecdotally reported to induce clinical and histologic remission of ulcerative colitis (UC) in two patients whose disease was refractory to multi-agent medical therapy.

Others and we have previously shown that bromelain removes certain cell surface molecules that affect lymphocyte migration and activation.  Bromelain treatment has also been shown to affect leukocyte activation and production of cytokines and inflammatory mediators.  We hypothesize that proteolytic removal of bromelain-sensitive molecules from T lymphocytes and colonic cells alters their adhesion and/or activation properties to decrease intestinal inflammation in IBD.

The specific aims of this study are: 1) To determine the efficacy of bromelain treatment in murine models of inflammatory bowel disease (IBD); and 2) To determine the effect of in vitro bromelain treatment on cellular activation and cytokine secretion in colon biopsies from normal human controls and IBD patients.  These studies will provide the scientific basis necessary to justify further mechanistic studies of bromelain activity as well as Phase I/II clinical trials of bromelain treatment in humans with IBD.  The use of oral proteases to modify inflammation in the gut is a novel approach that is likely to also yield additional insights into the pathogenesis and treatment of IBD.